加味茵陈四逆汤对胆道闭锁小鼠MMP9/TIMPs表达的影响
摘要
目的观察加味茵陈四逆汤对胆道闭锁模型小鼠基质金属蛋白酶9(MMP9)及其抑制剂TIMP1、TIMP2基因表达的影响。方法 SPF级Balb/c新生鼠随机分成空白组、模型组和加味茵陈四逆汤高、中、低剂量组。新生鼠于出生24h内腹腔注射30ul 106PFU/ml的恒河猴轮状病毒(rhesus monkey rotavirus,RRV)构建胆道闭锁模型。用药1周后,各组肝脏行HE染色,RT-qPCR检测肝组织MMP9 mRNA、TIMP1 mRNA、TIMP2 mRNA的表达。结果加味茵陈四逆汤各组比模型组体重稍增、黄染改善,肝脏汇管区炎症有所减轻;加味茵陈四逆汤高、中、低剂量组MMP9 mRNA的表达比模型组低,但无统计学意义(P>0.05);加味茵陈四逆汤高、低剂量组TIMP1 mRNA的表达比模型组低(P<0.01);加味茵陈四逆汤高、中、低剂量组TIMP2 mRNA表达比模型组减少(P<0.01)。结论加味茵陈四逆汤能有效地改善恒河猴轮状病毒诱导的胆道闭锁小鼠的症状,可能是通过下调TIMP1 mRNA和TIMP2 mRNA来发挥作用的。
引文
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[2] Verkade HJ,Bezerra JA,Davenport M,et al.Biliary atresia and other cholestatic childhood diseases:Advances and future challenges[J].J Hepatol,2016,65(3):631.
[3] De Minicis S,Seki E,Uchinami H,et al.Gene expression profiles during hepatic stellate cell activation in culture and in vivo[J].Gastroenterology,2007,132(5):1937.
[4] Xiao Y,Zhou Y,Chen Y,et al.The expression of epithelial-mesenchymal transition-related proteins in biliary epithelial cells is associated with liver fibrosis in biliary atresia[J].Pediatr Res,2015,77(2):310.
[5] Prystupa A,Boquszewska A,Bojarska A,et al.Activity of MMP-2,MMP-8 and MMP-9 in serum as a marker of progression of alcoholic liver disease in people from Lublin Region,eastern Poland[J].Ann Agric Environ Med,2015,22(2):325.
[6] Wielockx B,Lannoy K,Shapiro SD,et al.Inhibition of matrix metalloproteinases bloks lethal hepatitis and apoptosis induced by tumor necrosis factor and allows safe antitumor therapy[J].Nat Med,2001,7(11):1202.
[7] Ismail MH,Pinzani M.Reversal of hepatic fibrosis:pathophysiological basis of antifibrotic therapies[J].Hepat Med,2011,4(3):69.
[8] I Okazaki,T Noro,N Tsutsui,et al.Fibrogenesis and carcinogenesis in non-alcoholic steatohepatitis (NASH):involvement of matrix metalloprotein-ases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs)[J].Cancers,2014,6(3):1220.
[9] 许楷斯,许华,罗文,等.温阳活血化湿法治疗胆道闭锁手术后患儿的临床疗效分析[J].中医药导报,2016,22(2):61.
[10] 李洁,徐玉莲,罗书,等.加味茵陈四逆汤对实验性肝纤维化小鼠MMP1和TIMPs表达的影响[J].辽宁中医杂志,2016,43(6):1315.