摘要
目的:观察补肾化瘀方抗肝纤维化作用及对Hedgehog信号通路关键分子表达的影响,探讨其可能的作用机制。方法:采用CCl4皮下注射6周建立肝纤维化模型,同时以不同剂量补肾化瘀方干预6周。全自动生化仪检测血清肝功能(ALT、AST、TBil、ALP),碱水法检测肝组织匀浆羟脯氨酸含量,HE和Masson染色观察大鼠肝组织炎症和纤维化程度,RT-PCR和Western Blot技术检测肝组织中Hedgehog信号通路关键分子Shh、Ptch-1、Gli-1mRNA和蛋白表达。结果:模型组大鼠血清ALT、AST、TBil、ALP水平较正常组显著增高(P<0.01),肝组织炎症活动度和纤维化程度评分、羟脯氨酸含量较正常组显著升高(P<0.01),肝脏Shh、Gli-1 mRNA和蛋白表达均显著高于正常组(P<0.01),Ptch-1 mRNA和蛋白表达较正常组显著降低(P<0.01);应用补肾化瘀方干预后,血清肝功能水平、肝组织炎症活动度和纤维化程度评分、羟脯氨酸含量以及Shh、Gli-1 mRNA和蛋白表达有不同程度的下降(P<0.05,P<0.01)。结论:CCl4诱导的大鼠肝组织肝纤维化存在着Hh信号通路的激活,补肾化瘀方可能通过抑制Hedgehog信号通路的异常激活,防止肝纤维化的进一步进展。
Objective:To observe the effects of Bushen Huayu Decoction on the key molecules of the Hedgehog signaling pathway in hepatic fibrosis rat and to explore the possible mechanism.Methods:The model of hepatic fibrosis in rats was induced with 6 weeks of subcutaneous injection of CCl4,simultaneously,the rats were treated with different dosage of Bushen Huayu Decoction.The serum liver function was tested with automatic biochemical analyzer,the hepatic carboxy proline was tested with Caustic method,the inflammation and fibrosis in liver tissue were observed with HE and Masson stainings,the mRNA and protein expression of Shh,Ptch-1 and Gli-1,the key molecules of the Hedgehog signaling pathway in hepatic fibrosis rat were tested with RT-PCR and Western Blot.Results:The levels of serum ALT,AST,TBil and ALP in model rats were obviously higher than those in normal rats(P<0.01);the inflammation activity,fibrosis scoring of liver tissue and the carboxy proline content were obviously higher than those in normal rats(P<0.01);the expression of hepatic Shh,Gli-1 gene mRNA and protein were obviously higher than those in normal rats(P<0.01);the expression of hepatic Ptch-1 gene mRNA and protein were obviously lower than those in normal rats(P<0.01).After the treatment of Bushen Huayu Decoction,the serum liver function,the inflammation activity,fibrosis scoring of liver tissue and the carboxy proline content to varying degrees,the expression of hepatic Shh,Gli-1 gene mRNA and protein showed a decrease,respectively(P<0.05,P<0.01).Conclusion:Hepatic fibrosis in rats induced by CCl4 showed activation of the Hh signaling pathway.Bushen Huayu Decoction can prevent the further progress of liver fibrosis by inhibiting the abnormal activation of the Hedgehog signaling pathway.
作者
毛晓娟
陈芝芸
严茂祥
何蓓晖
王潇
余亚平
叶蕾
MAO Xiao-juan;CHEN Zhi-yun;YAN Mao-xiang;HE Bei-hui;WANG Xiao;YU Ya-ping;YE Lei(The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou310006,China;The Sixth People’s Hospital of Nantong,Nantong226011,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2019年第10期4557-4560,共4页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
浙江省自然科学基金项目(No.LY14H270010)~~
