http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/138 2026-04-03T21:18:18Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41297 標題: 龍葵葉子水萃物作用於鼠類巨噬細胞株RAW 264.7之抗發炎機制探討; Anti-inflammatory effects of Solanum nigrum Linn leaf water extracts (SNE leaf) in murine macrophage RAW 264.7 作者: Kuo-Hui Lin; 林國輝 摘要: Solanum nigrum Linn (SNL)，中文名稱為龍葵，他是屬於茄科家族的一位成員，在野外常常可以很容易地見到他的蹤跡。在傳統上，龍葵常常被用來當作中藥來使用，並且主要是用來治療發炎與癌症等疾病。根據統計，有百分之二十五左右的癌症被認為與慢性感染及發炎有關。在文獻中普遍認為由慢性發炎組織中的巨噬細胞所產生出來的活性氧分子(Reactive Oxygen Species，ROS)及活性氮分子 (Reactive Nitrogen Species，RNS)會對細胞內的DNA造成損傷，進而造成癌症的產生。而在這過程中，一些與製造活性氧分子及二十碳烯酸(Eicosanoid)相關的酵素[e.g. 第二型煙醯胺腺嘌呤二核苷酸磷酸氧化酶(NADPH Oxidase-2，NOX-2)，黃嘌呤氧化酶(Xanthine Oxidase，XO)，誘導型一氧化氮合成酶(inducible Nitric Oxide Synthase，iNOS)，第二型環氧合成酶(Cyclooxygenase-2，COX-2)]其調節上的異常已經被證實對此過程有很重要的影響。在巨噬細胞中，與這些酵素有關的訊息傳導途徑主要包含核轉錄因子-κB(Nuclear Factor-κB，NF-κB)、轉錄激活蛋白-1 (Activator Protein-1，AP-1)、促分裂素原活化蛋白激酶(Mitogen-Activated Protein Kinase，MAPK)等途徑。因此，透過研究一些具有抗發炎潛力的物質可能對在發炎及癌化等方面上的化學預防會有很重要的幫助。 為了探討龍葵水萃物其所具有的抗氧化及抗發炎效應，我們藉由XO活性測定法(Xanthine Oxidase activity assay)，發現到龍葵的葉子及綠果實水萃物部分對於黃嘌呤氧化酶的活性具有比較顯著的抑制能力，然而在莖的水萃物部分就沒有這樣的結果。另外也有使用亞硝酸鹽測定(nitrite assay)來檢測龍葵對於脂多醣 (Lipopolysaccharide，LPS)激活處理下的鼠類巨噬細胞RAW 264.7其一氧化氮釋放能力的影響。我們發現到僅有龍葵的葉子及綠果實水萃物具有抑制一氧化氮釋放的能力。除此之外我們還發現到僅有龍葵葉子的水萃物可以抑制脂多醣激活處理下的RAW 264.7細胞其活性氮分子產生的情形。從這裡我們可以推測龍葵葉子的水萃物可能就是藉由降低鼠類巨噬細胞RAW 264.7之一氧化氮、活性氮分子的生成並且抑制黃嘌呤氧化酶的活性來達到抗發炎的作用。另外還有使用西方墨點法(western blot)去分析龍葵葉子水萃物對於細胞內的發炎訊息傳導途徑影響情形。這邊的實驗結果顯示出龍葵葉子水萃物不但可以抑制細胞內的p38/JNK MAPK活性，同時也可以去降低NF-κB (p65)/AP-1 (phospho c-jun)的核移位(nucleus translocation)程度。在反轉錄聚合酶鏈鎖反應(RT-PCR)實驗中，我們還發現到龍葵葉子水萃物可以抑制脂多醣激活處理下的RAW 264.7細胞其iNOS mRNA的表現。; Solanum nigrum Linn (SNL), a member of the Solanaceae family , is a common herb that grows wildly and abundantly in open fields .Traditionally, it has been used in chinese medicine for curing inflammatory disease and various kinds of cancers. Approximately, 25 % of all cancers are somehow associated with chronic infection and inflammation. Chronic inflammation is considered as a possible mechanism in initiating tumorigenesis, resulting from the generation of ROS (Reactive Oxygen Species)/RNS (Reactive Nitrogen Species) by macrophages in the inflamed tissue and resulted in DNA damage. Chronic dysregulated activation of some cellular ROS/Eicosanoid generating enzymes, NOX-2 (NADPH Oxidase-2), XO (Xanthine Oxidase),iNOS (inducible Nitric Oxide Synthase) and COX-2 (Cyclooxygenase-2), have been shown to play pivotal roles during this process. The signal transduction pathways related to these enzymes in macrophages mainly including NF-κB/AP-1/MAPK pathway. Thus, to study the mechanism of the potential agents with anti-inflammatory activities might be important in the effects of chemoprevention of chronic inflammation and carcinogenesis. The main aim of this study is to evaluate the anti-oxidant and anti-inflammatory effects about Solanum nigrum Linn water extracts (SNE). Using the xanthine oxidase activity assay, we found that the stem water extracts of SNL didn't inhibit xanthine oxidase activity, but only the leaf and green fruit water extracts of SNL demonstrate the inhibitory activity. We also used the nitrite assay to investigate the inhibition ability of SNL on the nitrite released in culture medium of LPS-stimulated RAW 264.7 cells. We found that only the leaf and green fruit water extracts of SNL effectively inhibited the nitrite excretion. Additionally, the leaf water extracts of SNL effectively inhibited the ROS production in LPS-stimulated RAW 264.7 cells, but the stem and fruit water extracts of SNL didn’t. These results suggested that the leaf water extracts of SNL might exert the anti-inflammatory actions by suppressing NO and ROS production and xanthine oxidase activity. Moreover, we used western blot to investigate the inhibition ability of the leaf water extracts on the cellular inflammatory signal transduction pathway . The data demonstrated that the leaf water extracts greatly inhibited the p38/JNK MAPK activity , and also had the ability to decrease the NF-κB (p65)/AP-1 (phospho c-jun) nuclear translocation level. Then, we used RT-PCR to assay the iNOS mRNA expression, indicating that the leaf water extracts could inhibit iNOS mRNA expression dose-dependently. 2009-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66219 標題: 魚藤酮引起MCF-7乳癌細胞凋亡及兒茶素抑制CL1-5肺癌細胞轉移之機制探討; Mechanisms of Rotenone-induced Apoptosis in MCF-7 Human Breast Cancer Cells and Inhibition Effects of EGCG on Metastasis in CL1-5 Human Lung Cancer Cells 作者: Yea-Tzy Deng; 鄧雅姿 摘要: 中文摘要 癌症目前對全世界仍是一大威脅，更是台灣持續蟬聯十大死因的頭號殺手，因此，探討癌症的預防及治療方法仍是科學家孜孜不倦的課題。癌細胞由於具有持續增生及切割細胞外基質進而通過血管進入血液而轉移至其它組織的特性，因此，如何使細胞不再不斷增生及如何抑制細胞轉移至其他組織乃為癌症研究的首要目標。目前已有許多研究報告指出，植物中具有許多可以抑制癌細胞生長及轉移的天然物質，且由於癌症治療須耗費大量金錢，也因此，研究如何利用這些大自然天然的寶藏對抗人類的癌症疾病實為當務之急。魚藤酮存在於魚藤植物的根部，其會抑制粒線體內膜上電子傳遞鏈複合體 Ι (electron transfer chain complex Ι)造成細胞內活性氧 (reactive oxygen species; ROS) 的產生。魚藤酮最早於1930年代開始用來毒魚，於約150年前開始用於當作殺蟲劑。然而近年來的文獻指出，魚藤酮會引起黑色素瘤、白血病細胞凋亡。由於引起細胞凋亡乃為對抗癌細胞之重要步驟，又乳癌為威脅女性之惡性腫瘤，因此，我們極欲探討魚藤酮是否可引起乳癌細胞之細胞凋亡。在本論文中，我們利用methylthiazolyldiphenyl-tetrazolium bromide (MTT)試驗、trypan blue exclusion assay、alamar blue試驗、流式細胞儀、螢光顯微鏡觀察細胞核法，發現魚藤酮可引起人類乳癌細胞株MCF-7發生細胞凋亡的現象，此種結果隨著魚藤酮劑量和時間的增加而更明顯。進一步用西方點墨法分析和引起細胞凋亡現象有關的蛋白發現，魚藤酮可促使poly (ADP-ribose) polymerase (PARP) 活化、抗細胞凋亡現象的蛋白Bcl-2 表現下降、及促進細胞凋亡現象發生的蛋白Bax表現上升，並由觀察魚藤酮對粒線體膜電位的影響發現魚藤酮可改變粒線體膜電位差，更證實了魚藤酮確實會引起MCF-7細胞發生細胞凋亡。由於魚藤酮會抑制電子傳遞鏈複合體 Ι 而導致活性氧產生，我們發現隨著處以MCF-7細胞的魚藤酮濃度增高，確實會增加活性氧的產生。進一步利用西方點墨法研究魚藤酮於MCF-7細胞引起細胞凋亡所經過的訊息傳遞途徑，發現魚藤酮引起的活性氧增加會活化c-jun N-terminal kinase (JNK) 及p38 mitogen-activated protein kinase (p38 MAPK) 訊息傳遞，並降低extracellular signal-regulated protein kinase 1/2 (ERK 1/2) 訊息傳遞，進而引起細胞凋亡現象的發生。 另一方面，由於癌細胞轉移會導致癌症治療無法順利進行，因此研究如何抑制癌細胞轉移乃為癌症研究之重要課題。轉移是惡性程度高且預後差的癌症之特性，轉移的一個重要步驟是細胞分泌蛋白酶以切割細胞外的基質，使細胞能通過細胞外基質進入血液中，進而隨著血液轉移至其它組織。因此，促使過量細胞外基質的切割是癌細胞轉移的重要特徵，而扮演切割細胞外基質重要角色的是基質蛋白酶 (matrix metalloproteinases; MMPs)。由於肺癌持續為全世界致死率最高的癌症，且肺癌的高致死率是因其極具轉移的特性，因此我們選用具高轉移能力的肺癌細胞株CL1-5作為研究對象。又茶具有抗癌活性，因此，我們想探究綠茶中主要的茶多酚epigallocatechin-3-gallate (EGCG)是否可抑制高轉移性肺癌細胞株CL1-5轉移的能力。首先利用MTT試驗觀察EGCG對CL1-5細胞生長的影響，發現EGCG濃度高於20 μM時會抑制細胞生長，EGCG濃度於20 μM以下時細胞生長則無明顯影響。進一步探討EGCG於20 μM以上細胞生長的減緩是由於引起細胞凋亡或導致細胞週期停止，以流式細胞儀觀察的結果，EGCG於20 μM以上會導致細胞週期停止於G2時期，且並不會引起細胞凋亡現象的發生。接下來欲探討EGCG對CL1-5細胞轉移能力影響，利用轉移試驗發現EGCG 可抑制CL1-5細胞的轉移能力。由於MMP-2為降解細胞外基質的重要酵素，因此，若MMP-2的表現被抑制，則可抑制細胞降解細胞外基質的能力，進而抑制細胞轉移至其他組織。利用gelatin zymography、西方點墨法、聚合酶連鎖反應，發現EGCG會抑制CL1-5細胞內MMP-2 mRNA及蛋白的表現。進一步研究其中參與的訊息傳遞途徑，發現EGCG會抑制CL1-5細胞內JNK的訊息傳遞，導致MMP-2的轉錄因子NF-κB及Sp1無法由細胞質進入細胞核內進行MMP-2 mRNA的轉錄，而抑制MMP-2 mRNA的形成。觀察EGCG對MMP-2 promoter活性的影響，更證實了EGCG可抑制CL1-5細胞MMP-2 promoter的活性。又因臨床用藥docetaxel具有強副作用如白血球過低、貧血、腹瀉、掉髮，疲倦、虛弱等，因此，我們想探知並用臨床用藥及EGCG是否可減少臨床用藥劑量以期減少副作用的發生，結果指出並用docetaxel與EGCG可在較低劑量的docetaxel即可抑制MMP-2的表現。綜合我們的研究指出，茶中的EGCG及魚藤植物的魚藤酮對癌症預防扮演重要角色！; Cancer is still a serious problem in the world. Therefore, it is important to find ways to prevent or cure cancer. Because cancer cells possess abilities to prolong cell growth and invade to other tissues, it is still thorny to control cancer disease. Therefore, how to suppress cell growth in cancer cells and prevent cancer cells invade to other tissues is of great urgency. Phytochemicals are a group of compounds from natural plants. Recent reports show that they are bioactive components in natural plant to execute chemoprevention or other beneficial effects such as prevent diabetes, protect neuron cells and prevent obesity. Rotenone is a phytochemical from the roots of the Derris and Lonchorcarpus species. Rotenone is an inhibitor of electron transfer chain complex Ι (NADH dehydrogenase complex) and it can promote production of reactive oxygen species (ROS). It has been used as a botanical insecticide for at least 150 years to control crop pests and used even longer as a fish poison by native tribes in South America and East Africa. Recent reports show that rotenone can induce apoptosis in human melanoma cells and leukemia cells. Because anti-apoptosis plays an important role in anti-cancer, we want to determine whether rotenone can induce apoptosis in MCF-7 breast cancer cells which threaten women worldwide. In this study, we found that rotenone can induce apoptosis in MCF-7 human breast cancer cells by using MTT assay, trypan blue exclusion assay, alamar blue assay, flow cytometry and Hoechst 33258 staining and they are dose- and time-dependent effects. To further confirm these results, we used western blot analysis to investigate apoptosis-related proteins, PARP, Bcl-2 and Bax. We showed that rotenone can promote PARP cleavage, downregulate anti-apoptotic Bcl-2 and upregulate apoptotic Bax. In addition, rotenone can reduce mitochondria membrane potential. Because rotenone is attributed to irreversible binding and inactivation of mitochondrial electron transport chain complex Ι, we investigated whether rotenone indeed promote production of ROS in MCF-7 cells. Rotenone can result in an increase of the reactive oxygen species (ROS). We treated MCF-7 cells with rotenone and indeed found that ROS was increased. Then, we want to determine the signaling pathways under treatment of EGCG in MCF-7 cells. Using western blotting analysis, we found that rotenone induced JNK and p38 activation, whereas it attenuated ERK1/2 activation. Then, apoptosis was induced. In addition, metastasis is a fundamental property of high malignant cancer cells with poor clinical outcome. Therefore, to investigate how to suppress metastasis is an important urgency. Cleavage of extracellular matrix to allow cells invade into blood and transfer to other tissues is an important step in metastasis and MMPs play important roles in this step. Because lung cancer has the highest rate of cancer mortality worldwide and the highest rate of lung cancer mortality is due to their high potential of metastasis, we used highly invasive CL1-5 human lung cancer cells to investigate possible mechanisms of suppression tumor invasion in cancer cells. Green tea contains anti-cancer effects, so we want to determine whether EGCG, the major bioactive compound in green tea, can attenuate metastasis in highly invasive CL1-5 human lung cancer cells. First, we found that EGCG suppress cell growth at concentration higher than 20 μM by using MTT assay. Further, we want to investigate whether EGCG induce apoptosis or cell cycle arrest at concentrations higher than 20 μM. We used flow cytometry analysis and found that EGCG induced G2/M arrest in CL1-5 cells at concentrations of 30, 40 and 50 μM. Next, we want to investigate whether EGCG can attenuate invasion ability of CL1-5 cells. Using transwell invasion assay, EGCG could suppress invasion of CL1-5 cells. Because MMP-2 plays important roles to degrade extracellular matrix and is closely related to invasion in patients of lung cancer, we want to investigate whether EGCG can affect expression of MMP-2 in CL1-5 cells. Using gelatin zymography, western blot analysis and PCR, we found that EGCG can repress MMP-2 expression at the transcriptional level. Furthermore, by western blot analysis we showed that EGCG could suppress activation of JNK and attenuate translocation of MMP-2 transcription factor, NF-κB and Sp1, from the cytosol into the nucleus. In addition, docetaxel, a clinical drug used in the treatment of lung cancer, performs serious side effect, we want to clarify synergistic effects of EGCG and docetaxel. Combine EGCG and docetaxel can repress MMP-2 expression at low dosages of docetaxel. Taken together, rotenone and EGCG may be potential phytochemicals to chemoprevent breast cancer and lung cancer respectively and they may play synergistic effects with clinical drug. 2012-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30189 標題: 魚藤酮對MCF7乳癌細胞株引起的細胞凋亡現象之機制探討; Mechanisms of Rotenone-induced Apoptosis in MCF7 Human Breast Cancer Cells 作者: Yea-Tzy Deng; 鄧雅姿 摘要: Rotenone天然存在於豆科植物Derris根部，rotenone可以抑制粒線體內膜上電子傳遞鏈複合物Ι (electron transfer chain complex Ι)，而引起細胞凋亡(apoptosis)現象。Rotenone所引起的細胞凋亡早被認知，然而rotenone所引起的細胞凋亡現象究竟是經由什麼機制並不是很清楚。在本篇研究中，我們發現rotenone可以促使人類乳癌細胞MCF7細胞生長率下降、細胞死亡率上升，此種結果隨著rotenone劑量和時間的增加而更明顯。以流式細胞儀分析細胞內DNA含量和對細胞核內之染色質進行染色，可得知rotenone確實可以使MCF7細胞發生細胞凋亡現象。用流式細胞儀進一步分析，發現rotenone會使細胞內粒線體內膜的跨膜電位消失且會促使活性氧(ROS)產生。再用西方點墨法分析和引起細胞凋亡現象有關的蛋白質procaspase-9、 PARP、 Bcl-2、及Bax，我們發現rotenone可以促使procaspase-9、 PARP被活化，抗細胞凋亡現象的蛋白質Bcl-2 表現下降，及促進細胞凋亡現象發生的蛋白質Bax表現上升。由這些結果可以得知，rotenone所引起的細胞凋亡現象是和caspase及粒線體有關的。我們進一步研究rotenone所引起細胞凋亡所經過的訊息傳遞途徑，發現rotenone所引起的細胞凋亡現象是需要extracellular signal-regulated kinases (ERK1/2), N-terminal protein kinase (JNK)和p38 mitogen activated protein (MAP) kinase活化的。本篇研究結果發現rotenone可抑制乳癌細胞之生長，而rotenone是否能作為治療乳癌的有效物質，仍需進一步的動物試驗證明。; Rotenone, an inhibitor of NADH dehydrogenase complex, is a naturally occurring insecticide, and it is capable of inducing apoptosis. However, little is known about the mechanism for the induction of apoptosis by rotenone. Here we report that in vitro treatment of human breast cancer MCF7 cells with rotenone decreased cell viability and induced cell death in a dose- and time-dependent manner. DNA flow cytometric analysis and staining of nuclear chromatin indicated that rotenone actively induced apoptosis in MCF7 cells. Loss of mitochondrial transmembrane potential and reactive oxygen species (ROS) generation were also detected by flow cytometry. We used Western blot analysis to evaluate the apoptosis-related proteins in MCF7 cells. The levels of procaspase-9, poly (ADP-ribose) polymerase (PARP), and Bcl-2 were decreased in a time-dependent manner, while the level of Bax was increased. These findings suggest that rotenone-induced apoptosis may be a caspase- and mitochondrial-dependent pathway. Furthermore, rotenone treatment induces phosphorylation of extracellular signal-regulated kinases (ERK1/2), N-terminal protein kinase (JNK), and the p38 mitogen activated protein (MAP) kinase, indicated that ERK1/2, JNK and p38 MAP kinases are activated. Taken together, this study demonstrated rotenone as an inhibitory agent against human breast cancer MCF7 cells in vitro. Further in vivo studies are required to determine whether rotenone could be an effective chemotherapeutic agent for the management of breast cancers. 2007-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29666 標題: 魚油對於小鼠脂肪組織巨噬細胞堆積及發炎反應之影響研究; The Effect of Fish Oil Diet on Adipose Tissue Macrophage Accumulation and Inflammation in ob/ob Mice 作者: Ya-Fen Lai; 賴雅芬 摘要: 肥胖是導致胰島素抗拒及第二型糖尿病的危險因子。近年來研究顯示在遺傳或高脂飲食導致的肥胖鼠中，其脂肪組織會分泌細胞激素吸引巨噬細胞滲入至脂肪組織，導致脂肪組織中巨噬細胞(adipose tissue macrophage, ATM)的堆積，這些ATM大多會聚集在壞死的脂肪細胞周圍以清除其殘骸，並釋放前發炎性物質使脂肪組織產生慢性發炎反應，而進一步導致胰島素抗拒。 在動物實驗中已知魚油具有抗發炎的效果，並能減緩大鼠或小鼠中胰島素抗拒的現象，因此我們推測魚油可能會藉由降低ATM的含量來改善胰島素抗拒。第一次實驗係以9週齡ob/ob鼠為動物模式，將之分為三組，分別餵與低脂飼料(4%大豆油；LF組)、高豬油飼料(4%大豆油+20%豬油；Lard組)或高魚油飼料(4%大豆油+20%魚油；FO組)，飼養10.5週後FO組的體重、脂肪組織重量及血液中葡萄糖和膽固醇的濃度皆顯著低於Lard組，然而FO組ATM表面抗原的表現量卻和Lard組沒有差異，顯示魚油並不會降低ATM的含量，但魚油卻能減緩ob/ob鼠胰島素抗拒的現象，因此我們推測FO組中所含的ATM其特性和生理意義可能和Lard組中具發炎性的ATM有所不同。 為了進一步探討FO組中所含的ATM之生理意義，於是我們以7週齡的ob/ob鼠進行第二次實驗，將之分為四組，除了LF組、Lard組及FO組外，另新增一組添加Thiazolidinedione (TZD)藥物的高豬油飲食組(4%大豆油+20%豬油+0.0012% Rosiglitazone；Rosi組)作為參考。四組於飼養7週後，FO組的體重、脂肪組織重量及血液中葡萄糖和膽固醇的濃度皆顯著低於Lard組，而脂肪組織免疫組織染色及定量聚合; Obesity is a risk factor for the development of insulin resistance and type II diabetes. Recent studies suggest that the adipose tissues of genetic or high-fat diet induced obese mice secrete cytokines to recruit macrophage infiltration, which leads to adipose tissue macrophage (ATM) accumulation. The ATM will localize with necrotic adipocytes to phagocyte the debris, and release proinflammmatory cytokines to invoke inflammatory response in adipose tissue leading to insulin resistance. Fish oil is known to ameliorate insulin resistance and inflammation in rodents, so we speculated that fish oil diet might decrease ATM content to ameliorate insulin resistance. Based on the hypothesis, we studied the effect of high fat diet rich in lard or fish oil on macrophage accumulation in ob/ob mice. In the first experiment, 9-week old ob/ob mice were divided into three groups and were fed with low fat (LF, 4% soybean oil), high fat-lard (Lard, 4% soybean oil + 20% lard) or high fat-fish oil diet ( FO, 4% soybean oil + 20% fish oil) for 10.5 weeks. Final body weights, adipose weights, plasma glucose and cholesterol of FO group were significantly lower than that of Lard group. However, the expression level of ATM surface marker was not different between the FO and Lard groups, which indicated that fish oil did not decrease ATM content, although fish oil can ameliorate insulin resistance in ob/ob mice. We speculated that the characters and physiological significance of ATM in FO group might be different from that of Lard group. To further investigate the physiological significance of ATM accumulation in FO group, 7-week old ob/ob mice were divided into four groups and were fed with low fat, high fat-lard, high fat-fish oil or rosiglitazone (Rosi) supplemented high fat lard diet (4% soybean oil + 20% lard + 0.0012% rosiglitazone) in the second experiment. After 7 weeks of feeding, final body weights, adipose weights, plasma glucose and cholesterol of FO group were significantly lower than that of Lard group. From the result of immunochemistry and quantitative PCR, we confirmed that the ATM content in FO group was not different from that of Lard group, whereas rosiglitazone decreased the ATM content. Furthermore, TUNEL assay suggested that the content of apoptotic cells in adipose tissues of FO group was higher than that in adipose tissues of Lard group. Analysis of adipose tissue morphology revealed that the average size of adipocytes in FO group was smaller than that of Lard group. From above, we speculate that fish oil will promote apoptosis of large adipocytes thus recruit macrophage infiltration to phagocyte apoptotic cells. Unlike necrotic cells, apoptotic cells may not invoke inflammatory response. The expression level of inflammatory gene such as iNOS was significantly lower in FO group than that of Lard group, and the expression level of anti-inflammatory gene such as IL-10 was higher in FO group than that of Lard group. Taken together, the physiological significance of ATM in FO group is tending to phagocyte apoptotic cells, and the majority of ATM in FO group may have anti-inflammatory or less inflammatory character. In contrast, rosiglitazone decreases inflammatory ATM to ameliorate insulin resistance. The mechanism of insulin sensitivity improvement by rosiglitazone and fish oil is not the same. 2007-01-01T00:00:00Z