黄水枝醇提物对CCl4致小鼠肝纤维化的改善作用及其机制初探
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篇名: 黄水枝醇提物对CCl4致小鼠肝纤维化的改善作用及其机制初探
TITLE: Preliminary Study on Improvement Effect of Tiarella polyphylla Ethanol Extract on CCl 4-induced Hepatic Fibrosis in Mice and Its Mechanism
摘要: 目的:考察黄水枝醇提物(TPME)对四氯化碳(CCl4)致小鼠肝纤维化的改善作用,并初步探讨其可能的作用机制。方法:将60只雄性昆明种小鼠按体质量随机分为正常组、模型组、阳性对照组(秋水仙碱0.1mg/kg)和TPME低、中、高剂量组(250、500、1000mg/kg),每组10只。除正常组外,其余各组小鼠均腹腔注射20%CCl4橄榄油溶液诱导肝纤维化,每周2次,连续8周。从造模的第5周起,各给药组小鼠灌胃相应药液,正常组和模型组小鼠灌胃等体积生理盐水,每天1次,连续4周。末次给药12h后,称定各组小鼠肝脏质量并计算肝指数,检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(C-Ⅳ)、层粘连蛋白(LN)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)含量;采用Westernblot法检测肝组织中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β(1TGF-β1)和Smad3蛋白的表达水平;以苏木精-伊红(HE)、Masson染色后观察肝组织病理变化。结果:与正常组比较,模型组小鼠肝指数和血清中ALT、AST活性以及MDA、PC-Ⅲ、C-Ⅳ、LN、TNF-α、IL-6含量均显著升高,SOD活性显著降低(P<0.01),肝组织中α-SMA、TGF-β1和Smad3蛋白的表达水平均显著升高(P<0.01),镜下可见肝组织出现明显的纤维化病变。与模型组比较,阳性对照组和TPME各剂量组小鼠肝指数和血清中ALT、AST活性以及MDA、PC-Ⅲ、C-Ⅳ、LN、TNF-α、IL-6含量均显著降低,SOD活性均显著升高(P<0.05或P<0.01),肝组织中α-SMA、TGF-β1和Smad3蛋白的表达水平均显著降低(P<0.05或P<0.01),镜下可见肝纤维化病变均有不同程度的改善。与TPME低剂量组比较,TPME高剂量组小鼠血清中PC-Ⅲ、LN、IL-6含量和肝组织中TGF-β1、Smad3蛋白的表达水平均显著降低(P<0.05)。结论:TPME对CCl4诱导的小鼠肝纤维化具有一定的改善作用,该作用可能与抑制胶原合成、抑制氧化应激反应、降低炎症因子含量、下调α-SMA和TGF-β1/Smad信号通路相关蛋白的表达有关。
ABSTRACT: OBJECTIVE:To investigate the improvement effect of Tiarella polyphylla ethanol extract (TPME)on CCl 4-induced hepatic fibrosis in mice ,and to explore its possible mechanism preliminarily. METHODS :Totally 60 male Kunming mice were randomly divided into normal group ,model group ,positive control group (colchicine 0.1 mg/kg),TPME low-dose ,medium-dose and high-dose groups (250,500,1 000 mg/kg)according to body weight ,with 10 mice in each group. Except for normal group , other groups were given 20% CCl4 olive oil solution intraperitoneally to induce hepatic fibrosis ,twice a week ,for consecutive 8 weeks. From the fifth week after modeling ,administration groups were given relevant medicine intragastrically ,normal group and model group were given constant volume of normal saline intragastrically ,once a day ,for consecutive 4 weeks. Twelve hours after last administration ,the liver weight of mice in each group was measured and the liver index was calculated. The serum contents of ALT,AST,SOD,MDA,PC-Ⅲ,C-Ⅳ,LN,TNF-α and IL- 6 were determined. Western blot assay was used to detect the protein expression of α-SMA,TGF-β1 and Smad 3 in liver tissue. HE and Masson staining were used to observe the pathological changes of hepatic tissue. RESULTS :Compared with normal group ,the liver index ,the activities of ALT and AST and the contents of MDA , LN,PC- Ⅲ ,C- Ⅳ ,LN,TNF-α and IL- 6 in serum were increased significantly , while the activity of SOD was 6011) decreased significantly in model group (P<0.01);the protein expression of α-SMA,TGF-β1 and Smad 3 in liver tissues were hfjsznd8@126.com increased significantly (P<0.01). Obvious fibrosis lesions was observed in liver tissue. Compared with model group ,the live indexes ,the activities of ALT and AST ,the contents of MDA,PC-Ⅲ,C-Ⅳ,LN,TNF-α and IL-6 in serum were decreased significantly in positive control group and TPME groups , while the activities of SOD were increased significantly (P<0.05 or P<0.01). The protein expression of α-SMA,TGF-β1 and Smad3 in liver tissue were decreased significantly (P<0.05 or P<0.01),and liver fibrosis was improved to different extent. Compared with TPME low-dose group ,the contents of PC- Ⅲ,LN and IL- 6 in serum ,protein expression of TGF-β1 and Smad 3 in liver tissue were decreased significantly in TPME high-dose group (P<0.05). CONCLUSIONS :TPME can improve hepatic fibrosis induced by CCl 4 in mice ,the mechanism of which may be associated with the inhibition of collagen synthesis and oxidative stress,the reduction of inflammatory factors ,and the down-regulation of the expression α-SMA and relative proteins of TGF-β1/ Smad signal pathway.
期刊: 2021年第32卷第14期
作者: 黄甫静,张金娟,董莉,李雕,张春雷,廖尚高,何迅
AUTHORS: HUANG Fujing ,ZHANG Jinjuan ,DONG Li,LI Diao,ZHANG Chunlei ,LIAO Shanggao ,HE Xun
关键字: 黄水枝;肝纤维化;炎症反应;氧化应激;转化生长因子β1/Smad信号通路;小鼠
KEYWORDS: Tiarella polyphylla ;Hepatic fibrosis ;Inflammation response ;Oxidative stress ;TGF-β1/Smad signal pathway ;Mice
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