基于核苷酸结合寡聚化结构域样受体蛋白3炎症小体探讨天麻钩藤颗粒对肝阳上亢证肾损害的作用机制

Mechanism of Tianma Gouteng Granules against Kidney Damage in SHRs with Ascendant Hyperactivity of Liver Yang:Based on NLRP3 Inflammasome

目的:通过对大鼠血压、血清炎症介质及肾脏病理学切片的检测,探讨天麻钩藤颗粒对高血压大鼠肝阳上亢证肾损害的改善作用及机制。方法:取32只自发性高血压大鼠(SHRs),随机分为对照组、模型组、天麻钩藤颗粒组(中药组)、尼莫地平组(西药组),每组8只,其中模型组、中药组、西药组给予附子汤灌服进行肝阳上亢证造模,再分别给予蒸馏水、天麻钩藤颗粒、尼莫地平灌服14 d。6只正常SD大鼠作为空白组,空白组、对照组给予蒸馏水灌服42 d。干预前后分别测量血压,干预后进行血清炎症介质核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、胱天蛋白酶(Caspase)-1及肾脏病理学切片检测。结果:西药组干预后收缩压明显降低(P<0.05),余干预前后变化不明显(P>0.05);与正常组比较,对照组、模型组、中药组大鼠血清中NLRP3、ASC、Caspase-1水平均升高,中药组较对照组、模型组较低(P<0.05);与空白组比较,对照组、模型组、中药组、西药组均出现肾小球缺血性表现,肾小球固缩,部分肾小球纤维化和玻璃样变,肾小管萎缩、消失,其中中药组、西药组较对照组、模型组2组病变有所减轻。结论:天麻钩藤颗粒对自发性高血压大鼠肝阳上亢证肾损害具有改善作用,其作用机制可能与抑制NLRP3炎症小体合成有关。

Objective:This study aims to investigate the mechanism of Tianma Gouteng Granules against renal damage in hypertension rats with the pattern of ascendant hyperactivity of liver yang based on blood pressure,serum inflammatory factors,and kidney pathological sections.Methods:A total of 32 spontaneously hypertensive rats(SHRs)were randomized into control group,model group,Tianma Gouteng Granules group(Chinese medicine group),and nimodipine group(western medicine group),8 in each group.Fuzi Decoction was used(i.g.)to induce the pattern of ascendant hyperactivity of liver yang in the model group,Chinese medicine group,and western medicine group,respectively,and then they were separately treated with distilled water,Tianma Gouteng Granules,and nimodipine for 14 days.Six normal SD rats were treated as blank group,and the blank group and control group were given(i.g.)distilled water for 42 days.Blood pressure was measured before and after intervention.Serum inflammatory factors nucleotide-binding domain-like receptor protein3(NLRP3),apoptosis-associated speck-like protein containing CARD(ASC),and caspase-1 were detected and renal pathological sections were observed after intervention.Results:The systolic blood pressure was reduced in the western medicine group after intervention(P<0.05),and the variation in blood pressure after intervention was not significant in other groups(P>0.05).The serum levels of NLRP3,ASC,and caspase-1 in the control group,model group,and Chinese medicine group were higher than those in the blank group,and the levels in the Chinese medicine group were lower than those in the control group and the model group(P<0.05).Compared with the blank group,the control group,model group,Chinese medicine group,and western medicine group all showed glomerular ischemic manifestations,glomerular shrinkage,partial glomerular fibrosis and hyaline degeneration,and tubular atrophy and disappearance,and these pathological changes were milder in the Chinese medicine and western medicine groups than in the control and model groups.Conclusion:Tianma Gouteng Granules can relieve the kidney damage in SHRs with ascendant hyperactivity of liver yang possibly by inhibiting the synthesis of NLRP3 inflammasome.