目的: 臨床上有些報告顯示，十二指腸空腸繞道手術可能可以改善糖尿病血糖控制。並同時使非酒精性肝炎嚴重度減低，本研究的目的在探討是否來自十二指腸空腸繞道手術的非酒精性肝炎改善和胰島素敏感性，與肝臟纖維化的肝內星狀細胞活性是否相關。
實驗設計: 使用Wistar大白鼠，並以下列方式進行12周的飼養，共分為四組: 第一組，正常飲食(個數=6)；第二組, Methionine-Choline缺乏與高脂肪飲食(個數=6)；第三組，Methionine-Choline缺乏與高脂肪飲食並實行十二指腸空腸繞道手術(個數=6)；第四組，Methionine-Choline缺乏與高脂肪飲食並給予Pioglitazone (PGZ)，一種胰島素增進敏感性藥物(個數=6)。在12周以後,所有老鼠接受口服葡萄糖耐受性試驗，並記錄體重、飲食量、副睪與腎臟旁脂肪重量，並比較內臟脂肪細胞的大小。以H&E染色觀察肝組織脂肪沉積的情形與肝發炎嚴重度。老鼠並以心臟採血測其肝功能，三酸甘油酯、膽固醇、空腹血糖值、胰島素，也以ELISA測量TNF-α與IL-6測量肝臟的發炎反應。肝纖維化的嚴重度也以IHC染色觀察肝臟之星狀細胞α-SMA的表現，最後在以real-time PCR看在纖維化生成路徑中TGF-β 1的表現與在脂肪生成路徑中SREBP-1的表現。
結果: Methionine-Choline缺乏與高脂肪飲食確實可以誘發飲食模式的胰島素抗性與非酒精性肝炎的動物.這些動物中，H&E染色可以發現肝細胞內嚴重的脂肪堆積，而IHC染色也可以看到與肝纖維化相關之星狀細胞的α-SMA的表現。 但腸胃繞道手術跟PGZ藥物一樣，可以逆轉許多代謝上的病變，包括內臟脂肪的重量，脂肪細胞的大小，由口服葡萄糖耐受性試驗可以發現更好的血糖控制，更少肝臟脂肪堆積與肝臟α-SMA的表現。且real-time PCR可以發現纖維化生成路徑中TGF-β 1 mRNA的表現也會減弱。
結論: 十二指腸空腸繞道手術確實可以改善非酒精性肝炎，並且是和胰島素敏感性的改善與肝纖維化相關之星狀細胞的活性相關，而且纖維化生成路徑中TGF-β 1 mRNA的表現減低也有關係。

Purpose: In some clinical studies, duodenal-jejunal bypass surgery is observed to have better diabetic control and resolution of non-alcoholic steatohepatitis (NASH). The purpose of this study is to investigate whether the effect of duodenal-jejunal bypass on resolution of NASH is associated with insulin sensitivity and activity of hepatic stellate cells in liver tissue.
Experimental Design: The male Wistar rats are divided into 4 groups and treated as following designs for 12 weeks: Group 1, Normal chow (n=6); Group 2, Methionine-Choline-Deficient (MCD) / High Fat (HF) diet (n=6); Group 3, MCD/HF diet and Duodenal-jejunal bypass (DJB) surgery (n=6); Group 4, MCD/HF diet and Pioglitazone (PGZ), an insulin sensitizer. (n=6). After 12 weeks, these rats all received oral glucose tolerance tests (OGTT). The body weight, food intake, epidydimal fat and peri-renal fat weight were measured and the size of visceral adipocyte was compared. The severity of hepatic steatosis and inflammation of liver tissue was observed by H&E stain. Plasma ALT, triglyceride, total cholesterol, fasting glucose, insulin and cytokines including TNF-α (tumor necrosis factor-α), and interleukin-6 (IL-6) were estimated by ELISA. The severity of fibrosis was determined by the expression of alpha-smooth muscle actin (α-SMA) in hepatic stellate cells by IHC stain. The mRNA expressions of fibrogenic gene, TGF-β 1 (Transforming growth factor-beta 1) and lipogenic gene, SREBF-1 (Sterol regulatory element-binding factor-1) were also examined by real-time PCR.
Results: MCD/HF diet induced a dietary rat model of insulin resistance and development of NASH. In these MCD/HF dietary rats, H&E stain showed severe hepatic steatosis, ballooning of hepatocytes. IHC stain revealed high expression of α-SMA by hepatic stellate cells for liver fibrosis. However, duodenal-jejunal bypass surgery and pioglitazone both can reverse the majority of metabolic changes such as visceral fat weight, decreased size of adipocytes, better glucose control on OGTT, decreased IL-6, less severe hepatic steatosis and liver fibrosis in morphology and IHC stain for α-SMA expression. Real-time PCR also showed declined mRNA expressions of TGF-β1 in fibrogenesis pathway after bypass surgery as well as in PGZ treatment.
Conclusion: Reduction of the severity of NASH from duodenal-jejunal bypass is associated with improvement of insulin sensitivity and down-regulation of the activity of hepatic stellate cells for liver fibrosis. Inflammation reaction of liver was also declined after bypass surgery. The mechanism is also associated with the decreased expression of TGF-β 1 in fibrogenesis pathway.
Keywords: Insulin sensitivity, Non-alcoholic steatohepatitis, Duodenal-jejunal bypass.

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