脉络宁口服液对动脉硬化性闭塞症大鼠的影响  

Exploring the effect of Mailuoning oral liquid on rats with arteriosclerotic occlusion

作　　者：来兴兆 范玲玲 黄素清 黄聪聪 李剑 谭宁华[1] LAI Xing-zhao;FAN Ling-ling;HUANG Su-qing;HUANG Cong-cong;LI Jian;TAN Ning-hua(School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China;Jinling Pharmaceutical Co.,Ltd.,Nanjing 210009,China)

机构地区：[1]中国药科大学,江苏南京211198 [2]金陵药业股份有限公司,江苏南京210009

出　　处：《时珍国医国药》2025年第1期17-24,共8页Lishizhen Medicine and Materia Medica Research

基　　金：金陵药业股份有限公司企业合作项目(校合2020-中003,校合2023-中067)。

摘　　要：目的基于NFAT5/NLRP3信号通路探究脉络宁口服液对动脉硬化性闭塞症(arteriosclerosis occlusion,ASO)大鼠的影响。方法采用股动脉损伤联合高脂饲料饲养75 d构建大鼠ASO模型,将造模大鼠随机分为模型组、脉络宁口服液低和高剂量组、脉络宁注射液组、阿托伐他汀钙组与KRN2(NFAT5抑制剂)组,连续给药14 d,每组5只动物;HE染色观察股动脉病理改变;试剂盒检测大鼠血浆中血脂、UA及HMGB1水平;Q-PCR法检测主动脉内皮功能障碍、肝脏组织脂代谢与炎症相关指标的mRNA水平;WB法检测肝脏组织中NFAT5/NLRP3信号通路的蛋白表达。结果ASO大鼠较对照组股动脉内膜增生且管腔狭窄,血浆TC、TG、LDL-C、UA、HMGB1及主动脉和肝脏组织HMGB1、RAGE、MCP-1、NLRP3、NFAT5、MMP9、MKP-1和ACLS1的mRNA水平均升高(P<0.01),肝脏组织NFAT5/NLRP3信号通路激活(P<0.01);脉络宁口服液与KRN2能改善ASO大鼠股动脉内膜损伤,抑制血浆、主动脉、肝脏组织中上述各指标升高(P<0.05,P<0.01)。结论脉络宁口服液可能通过减轻内皮损伤、调节肝脏脂代谢、降低炎症反应治疗ASO,其作用机制可能与抑制NFAT5/NLRP3信号通路密切相关。Objective To explore the effect of Mailuoning oral liquid(MOL)on arteriosclerotic occlusion(ASO)rats by regulating the NFAT5/NLRP3 signaling pathway.Methods The rat model of ASO was established by femoral artery injury combined with high-fat diet feeding for 75 days.The ASO rats were randomly divided into the model group,the MOL low-dose and high-dose groups,Mailuoning injection(MI),the atorvastatin calcium group and the KRN2(NFAT5 inhibitor)group,and each group with 5 rats was administered continuously for 14 days.HE staining was used to observe the pathological changes of femoral artery.Kits were used to detect the levels of blood lipid,UA and HMGB1 in plasma of ASO rats.Q-PCR was adopted to detect the mRNA expressions of the indicators related to aortic endothelial dysfunction,hepatic lipid metabolism disorder and inflammation.Western blot(WB)was utilized to detect the protein expressions of the NFAT5/NLRP3 signaling pathway in the liver tissues of ASO rats.Results Results showed that the intimas of femoral arteries were proliferated and the vascular lumina of femoral arteries were narrowed in ASO rats.The levels of TC,TG,LDL-C,UA and HMGB1 in plasma and the mRNA expressions of HMGB1,RAGE,MCP-1,NLRP3,NFAT5,MMP9,MKP-1 and ACLS1 in the aorta and liver tissues of ASO rats were significantly higher than those of control group(P<0.01).The NFAT5/NLRP3 signaling path⁃way in the liver tissues of ASO rats were activated(P<0.01).The intimal injury of femoral artery in the MOL and KRN2 rats were ameliorated.The increase of the above indicators in plasma,aorta and liver tissues in ASO rats were inhibited after treated by MOL and KRN2(P<0.05,P<0.01).Conclusion MOL may treat ASO by reducing endothelial injury,regulating liver lipid metabolism and blood lipid level,and reducing inflammatory reaction.The mechanism may be closely related to the inhibition of the NFAT5/NLRP3 signaling pathway.

关 键 词：动脉硬化性闭塞症大鼠模型 脉络宁口服液 NFAT5/NLRP3信号通路 炎症 脂代谢 

分 类 号：R285.5[医药卫生—中药学]