二氯醋酸二异丙胺抗肝纤维化作用的实验研究-普通外科学专业论文.docxVIP

中文摘要 二氯醋酸二异丙胺抗肝纤维化作用的实验研究 结论：1.DPDA 对肝星状细胞的增殖有明显抑制作用，低浓度时对正常肝细胞的 增殖有促进作用。 2.DPDA 对 CCl4 诱导纤维化小鼠模型的纤维化有逆转作用。 3.DPDA 成为临床抗肝纤维化药物有一定可能性。 关键词：二氯醋酸二异丙胺；肝纤维化；肝星状细胞； 研究生 ：颜晨 指导老师：江勇 Experimental study on the effect of anti-hepatic fibrosis of Diisopropylamine Dichloroacetate Abstract Experimental study on the effect of anti-hepatic fibrosis of Diisopropylamine Dichloroacetate Abstract Objective: 1.To study the effect of diisopropylamine dichloroacetate (DPDA) on the proliferation of LX2 and LO2 cells in vitro. 2.To investigate the fibrosis reverse effect of DPDA to CCl4-induced hepatic fibrosis mice in vivo. Method: 1. In vitro, MTT assay was used to determine the growth inhibition of LX2 and LO2 cells, and Western Blot was performed to investigate the indicators related to hepatic fibrosis. 2. In vivo, fifty male C57BL/6 mice were randomly allocated to three groups, the control group (n=10), the CCl4 group (n=30) and the DPDA+CCl4 group (n=10). The model of liver fibrosis was induced by intraperitondal injection with CCl4 (2 ul/g body weight dissolved 1:3 in corn oil) two times per week lasting for 12 weeks in CCl4 group and the DPDA+CCl4 group. After 8 weeks injection with CCl4, mice were taken DPDA by intragastric administration in DPDA+CCl4 group. Meanwhile, mice in CCl4 group were only taken PBS by intragastric administration. The degree of liver fibrosis was assessde by HE and Masson’s staining. Meanwhile, PCR、Immunohistochemistry、Western Blot were used to detect mRNA and protein levels of alpha-sooth muscle actin (α-SMA)、desmin、 Ki67、transforming growth factor-beta 1 (TGF-β1)、fibronectin (FN)、type I collagen. Results: After DPDA was added to LX2 and LO2 for 48h, DPDA could inhibit its proliferation, IC50 was （ 13.2±0.71 ） mmol/l; however, DPDA could facilitate the proliferation of LO2 when the concentration was below 1 mmol/l; difference between the groups was statistically significant (P0.05). HE and Masson stain showed that liver dama