凝血酶經由經由Src誘導人類牙齦纖維母細胞表現α-SMA

Abstract

緒論：藥物引起的牙齦過度生長常因為無法換藥而難以從根本改善，因此手術切除術成為較常使用的方法。但手術後的復發率高，除了藥物本身的影響，傷口處會有大量的凝血酶聚集，除了幫助止血，傷口癒合外，也可能在此好發牙齦腫大的族群中，造成過度的細胞間質堆積，而造成再發率居高不下。研究目的：利用人類牙齦纖維母細胞，以凝血酶誘導，觀察肌纖維母細胞纖維化的標記物α型平滑肌肌動蛋白(α-SMA)的表現，並尋找可抑制此反應的抑制劑。材料與方法：本實驗利用人類牙齦纖維母細胞，以凝血酶處理細胞，以西方墨點法檢測α-SMA，並以不同的抑制劑(PP2, EGCG, lovastatin, and curcumin)合併凝血酶處理細胞，觀察α-SMA表現量的變化。結果：凝血酶會誘導人類牙齦纖維母細胞中α-SMA的表現，且使用的Src family抑制劑PP2及天然抑制劑 (EGCG and curcumin)及降血脂藥物(lovastatin)可有效抑制凝血酶所誘導的α-SMA表現。結論：凝血酶會經由Src誘導人類牙齦纖維母細胞中α-SMA的表現，EGCG、lovastatin和curcumin可抑制其表現。

Introduction: The best way to treat drug-induced gingival overgrowth (DIGO) is changing medication. But we often encounter the situation that we can’t change the medication. In the situation, surgical intervention by gingivectomy or flap operation is the resolution of DIGO. However, the recurrence rate is high even under intensive follow up and good oral hyginene. Beside the effect of the medication, activation of thrombin around the wound, in addition to the function of hemostasis and wound healing, may also cause overdeposition of the extracellular matrix and the high recurrance rate of DIGO. Purpose: To observe the expression of alpha smooth muscle actin (α-SMA), marker of myofibroblast and fibrotic activity, after the treatment of thrombin in human gingival fibroblasts. Then to try to find the inhibitor to inhibit this reaction. Material and method: Using Western blotting technique for analysis of α-SMA after treatment of thrombin in human gingival fibroblasts. Then after additional pre-treatment of the inhibitors (PP2, EGCG, lovastatin and curcumin), to observe the expression of α-SMA induced by thrombin. Result: Thrombin induces the expression of α-SMA. And the Src family inhibitor(PP2), natural inhibitors (EGCG and curcumin) and drug for cholesterol-lowering (lovastatin) can inhibit the expression of α-SMA induced by thrombin. Conclusion: Thrombin induced the expression of α-SMA through Src in human gingival fibroblasts. And it can be inhibited by EGCG, lovastatin and curcumin.