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基于NLRP3/Caspase-1信号通路探讨柴芍实脾汤抗大鼠急性肝损伤的作用机制

Mechanism of Chaishao Shipi Decoction Treating Acute Liver Injury in Rats Based on NLRP3/Caspase-1 Signaling Pathway
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摘要 目的:观察柴芍实脾汤对四氯化碳(carbon tetrachloride,CCl 4)诱导的急性肝损伤(acute liver injury,ALI)大鼠肝功能的影响,并基于NOD样受体热蛋白结构域包含蛋白3(nod-like receptor,pyrin domain containing 3,NLRP3)/天冬氨酸半胱氨酸蛋白酶-1(cysteinyl aspartate specific proteinase-1,Caspase-1)信号通路探讨相关作用机制。方法:36只SD大鼠随机分为对照组、模型组、柴芍实脾汤低剂量组(17 g·kg-1)、中剂量组(34 g·kg-1)、高剂量组(68 g·kg-1)及葵花护肝片组(0.921 g·kg-1),每组6只。各组连续给药2周,每日1次,对照组和模型组大鼠灌胃生理盐水。末次给药2 h后,除对照组外,其余大鼠灌胃CCl 4橄榄油溶液制备ALI模型。采用生化分析仪检测血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)含量,ELISA法检测血清白细胞介素-18(interleukin-18,IL-18)、白细胞介素-1β(interleukin-1β,IL-1β)含量,HE染色观察肝脏病理学形态,Masson染色观察肝脏纤维化程度,Western blot检测肝脏NLRP3、Caspase-1、IL-1β蛋白表达水平。结果:与对照组比较,模型组大鼠肝脏质量、肝脏指数增加(P<0.05);与模型组比较,柴芍实脾汤各个剂量组和葵花护肝片组大鼠肝脏质量、肝脏指数降低(P<0.05)。与对照组比较,模型组大鼠血清ALT、AST、IL-18、IL-1β含量升高(P<0.05);与模型组比较,柴芍实脾汤各个剂量组和葵花护肝片组大鼠血清ALT、AST、IL-18、IL-1β含量降低(P<0.05)。对照组大鼠肝小叶分布均匀,无明显纤维化;模型组大鼠肝细胞大面积脂质脱失,部分变性坏死,伴有胶原纤维沉积;与模型组比较,柴芍实脾汤各个剂量组和葵花护肝片组大鼠肝脏损伤明显改善,纤维化程度减轻。与对照组比较,模型组大鼠肝脏病理学评分和胶原沉积分数升高(P<0.05);与模型组比较,柴芍实脾汤各个剂量组和葵花护肝片组大鼠肝脏病理学评分、胶原沉积分数降� Objective:To observe the effect of Chaishao Shipi Decoction on liver function in rats with acute liver injury(ALI)induced by carbon tetrachloride(CCl 4),based on NOD-like receptor,pyrin domain containing 3(NLRP3)/The mechanism of action of cysteinyl aspartate specific proteinase-1(Caspase-1)signaling pathway was explored.Methods:Thirty-six SD rats were randomly divided into control group,model group,Chaishao Shipi Decoction low-dose group(17 g·kg-1),medium-dose group(34 g·kg-1),high-dose group(68 g·kg-1)and sunflower liver protection tablet group(0.921 g·kg-1),with 6 rats in each group.Each group was administered continuously for 2 weeks,once a day,and rats in the control group and model group were given normal saline.Two hours after the last administration,except for the control group,the rest of the rats were given CCl 4 olive oil solution to prepare the ALI model.The serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected by biochemical analyzer,and the serum levels of interleukin-18(IL-18)and interleukin-1β(IL-1β)were detected by ELISA.HE staining was used to observe the pathological morphology of the liver,Masson staining was used to observe the degree of liver fibrosis,and Western blot was used to detect the expression levels of NLRP3,Caspase-1 and IL-1βproteins.Results:Compared with the control group,the liver mass and liver index of the model group increased significantly(P<0.05).Compared with the model group,the liver mass and liver index of rats in each dose group and Sunflower Liver Protection Tablets group decreased significantly(P<0.05).Compared with the control group,the serum levels of ALT,AST,IL-18 and IL-1βin the model group increased significantly(P<0.05).Compared with the model group,the serum levels of ALT,AST,IL-18 and IL-1βin each dose group and Sunflower Liver Protection Tablets group decreased significantly(P<0.05).The liver lobules in the control group were evenly distributed and there was no obvious fibrosis.In the model group,the rat hepato
作者 娄静 余晓珂 赵雷 朱岩洁 袁帅强 王菲 张杭洲 徐娇娇 侯留法 LOU Jing;YU Xiaoke;ZHAO Lei;ZHU Yanjie;YUAN Shuaiqiang;WANG Fei;ZHANG Hangzhou;XU Jiaojiao;HOU Liufa(Henan Provincial Hospital of Integrative Medicine,Zhengzhou Henan China 450000;The Third Affiliated Hospital to Henan University of Chinese Medicine,Zhengzhou Henan China 450008)
出处 《中医学报》 CAS 2024年第10期2169-2175,共7页 Acta Chinese Medicine
基金 河南省中医药科学研究专项课题项目(2022ZY1147,2023ZY2139)。
关键词 柴芍实脾汤 葵花护肝片 急性肝损伤 NLRP3/Caspase-1信号通路 CCl 4 大鼠 Chaishao Shipi Decoction Sunflower Liver Protection Tablet acute liver injury NLRP3/Caspase-1 signaling pathway CCl 4 rat
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