基于NOD样受体3/嘌呤能受体P2X7通路探讨芪蛭真武汤对盐敏感高血压肾病大鼠的机制  

Mechanism of Qizhi Zhenwu Decoction on Salt-sensitive Hypertensive Nephropathy Rats Based on NOD-like Receptor Protein 3/Purinergic Receptor P2X7 Pathway

作　　者：李兆雯 马程程 谭颖颖[1] LI Zhao-wen;MA Cheng-cheng;TAN Ying-ying(Department of Typhoid and Golden Chamber,Shaanxi University of Chinese Medicine,Xianyang Shaanxi 712046)

机构地区：[1]陕西中医药大学伤寒金匮教研室,陕西咸阳712046

出　　处：《世界中西医结合杂志》2023年第2期264-270,276,共8页World Journal of Integrated Traditional and Western Medicine

基　　金：国家自然基金项目(81873296)。

摘　　要：目的基于NOD样受体3(NLRP3)/嘌呤能受体P2X7(P2RX7)通路探讨芪蛭真武汤对盐敏感高血压肾病大鼠的机制。方法选取Dahl/SS盐敏感大鼠28只,按随机数字表法分为模型组、芪蛭真武汤高、常剂量组和阳性对照组,每组各7只,SS-13BN盐不敏对照大鼠(含有肾素基因13号染色体替换的大鼠)7只(空白对照组)。各组大鼠行HE和Masson染色和免疫组化反应。记录动物一般状态观察,肾脏指数,全自动生化分析仪检测血清肌酐、尿素氮,Western blot检测蛋白表达。结果与空白对照组比较,模型组大鼠血压明显升高,与模型组比较,中药不同剂量治疗组血压水平降低,其中阳性对照组呈现血压下降趋势;真武汤高剂量组治疗28 d后血压水平明显降低,差异有统计学意义(P<0.05);真武汤常剂量组治疗第14、21天后血压水平明显降低,差异有统计学意义(P<0.05);与空白对照组大鼠24 h尿蛋白、尿素氮和肌酐比较,模型组明显升高,差异有统计学意义(P<0.05);芪蛭真武汤高、常剂量组和阳性对照组较模型组有不同程度降低,常剂量组下降,差异有统计学意义(P<0.05);模型组较对照组肾间质增宽,肾小管出现散在的空泡状,有部分蓝色胶原纤维沉积;芪蛭真武汤高、常剂量组和阳性对照组胶原纤维沉积分数较模型组明显降低,差异有统计学意义(P<0.05);与空白对照组比较,模型组NLRP3、P2RX7、CCL2和IL-1β蛋白水平明显升高,差异有统计学意义(P<0.05);芪蛭真武汤高、常剂量组和阳性对照的NLRP3、P2RX7、CCL2和IL-1β蛋白表达较空白对照组明显降低,差异有统计学意义(P<0.05),芪蛭真武汤常剂量组明显升高,差异有统计学意义(P<0.05)。结论对盐敏感高血压肾病大鼠应用芪蛭真武汤治疗,可有效改善大鼠肾组织病理损害,通过调控P2RX7/NLRP3通路降低大鼠炎症指标,改善盐敏感高血压肾病大鼠症状,以常剂量芪蛭真武汤效果最佳。Objective To explore the mechanism of Qizhi Zhenwu Decoction(QZZWD)on salt-sensitive hypertensive nephropathy rats based on NOD-like receptor protein 3(NLRP3)/purinergic receptor P2X7(P2RX7)pathway.Methods Twenty-eight Dahl/SS salt-sensitive rats were selected and divided into model group,QZZWD high dose group,QZZWD normal dose group,and positive control group according to random number table,with 7 in each group.Another 7 SS-13BN salt-insensitive rats(with replacement of chromosome 13 containing renin gene)were used as blank control group.The rats in each group were subjected to HE staining,Masson staining and immunohistochemical reactions,and the general state and kidney index were recorded.Serum creatinine and blood urea nitrogen were detected by automatic biochemical analyzer.Protein expression was detected by Western blot.Results Compared with the blank control group,the model group had significantly increased blood pressure,which was reduced by different doses of Chinese medicine,and the blood pressure of the positive control group presented a downward trend.The blood pressure of patients was reduced after 28 days of treatment with high dose of QZZWD(P<0.05),while QZZWD at a normal dose exerted a decreasing effect on the blood level after 14 days and 21 days of treatment(P<0.05).Compared with the conditions in the blank control group,the 24h urine protein,blood urea nitrogen and creatinine in the model group were increased(P<0.05),and compared with the model group,the QZZWD high and normal dose groups and the positive control group had a decrease to varying degrees,while the decrease in the QZZWD normal dose group was statistically significant(P<0.05).The model group had wider renal interstitium,and scattered vacuoles appeared in renal tubules,with some blue collagen fibers deposited as compared with the blank control group,while high and normal doses of QZZWD and positive drug reduced the collagen fiber deposition(P<0.05).Compared with the conditions in the blank control group,the protein levels of NLRP3,P

关 键 词：P2X7 NLRP3 芪蛭真武汤 盐敏感高血压肾病大鼠 

分 类 号：R285.5[医药卫生—中药学]