肾气丸对肾阳虚证大鼠水液代谢紊乱的调控作用  

Regulation effect of Shenqi Pills on water and fluid metabolism disorder in kidney-yang deficiency rats

作　　者：张叶慧 缪睿 黄筠皓 魏佳乐 王思晨 李昌煜[1] ZHANG Yehui;MIU Rui;HUANG Junhao;WEI Jiale;WANG Sichen;LI Changyu(School of Pharmacology,Zhejiang Chinese Medical University,Hangzhou 310000,China)

机构地区：[1]浙江中医药大学药学院,杭州310000

出　　处：《中华中医药杂志》2023年第9期4382-4386,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82074304)。

摘　　要：目的:明确肾气丸对肾阳虚证大鼠水液代谢紊乱的调控作用,初步探索其作用机制。方法:将40只SD大鼠随机分为正常组、模型组、肾气丸低剂量组和肾气丸高剂量组,每组10只。模型组及给药组给予200 mg·kg^(-1)·d^(-1)腺嘌呤悬浊液连续灌胃20 d,其中两给药组从实验第15天开始,连续灌胃1.5、3.0 g/kg肾气丸14 d。观察大鼠一般状况、症状体征(体质量、肛温、饮水量、尿量、脱毛、拱背、蜷缩及抓取激惹反应);收集大鼠24 h尿液,Elisa法测定17羟皮质类固醇(17-OHCS)含量;心脏取血,取小鼠下丘脑、肾髓质组织并匀浆,全自动生化仪测定大鼠肾功能指标,Elisa法测定血清促肾上腺皮质激素(ACTH)、皮质醇(CORT)含量,下丘脑血管加压素(AVP)、促肾上腺皮质激素释放因子(CRH)含量,血管加压素V2受体(V2R)、糖皮质激素受体-α(GCR-α)、水通道蛋白2(AQP2)、环磷酸腺苷酸(cAMP)、蛋白激酶A(PKA)含量。HE和Masson染色观察肾组织变化。结果:与模型组比较,肾气丸高剂量组能显著提高大鼠体质量(第21、28天)、肛温(P<0.05,P<0.01),减少饮水量与尿量(P<0.01),升高大鼠下丘脑CRH、血清ACTH、CORT和尿17-OHCS含量(P<0.01),并明显改善肾损伤病理与肾功能指标。肾气丸高剂量组显著提高大鼠下丘脑AVP含量、肾髓质GCR-α、V2R、cAMP、PKA和AQP2含量(P<0.01)。结论:肾气丸改善肾阳虚大鼠水液代谢紊乱可能是通过调控AVP-V2R-cAMP-PKA-AQP2通路实现的。Objective:To clarify the regulatory effect of Shenqi Pills on the disorder of water and fluid metabolism in rats with kidney-yang deficiency,and to preliminarily explore its mechanism.Methods:A total of 40 SD rats were randomly divided into four groups:normal group,adenine model group,low-dose Shenqi Pills group and high-dose Shenqi Pills group,10 rats in each group.200 mg·kg^(-1)·d^(-1)adenine suspension for 20 days was intragastrically given to model group and medication group to establish kidney-yang deficiency rat model.On the 15th day of adenine administration,the giving drug groups started to be administrated with Shenqi Pill,respectively(1.5,3.0 g/kg)for 14 consecutive days.The general conditions,symptoms and signs(weight,and temperature,drinking,urination,depilation,arching,curling and grabbing irritation)were observed.The 24 h urine of rats was collected,the content of 17-hydroxycorticosteroid(17-OHCS)was determined by Elisa.Blood was collected from the heart,the hypothalamus and kidney medulla tissues of mice were homogenized,the renal function indexes of rats were determined by automatic biochemical analyzer,and the contents of serum adrenocorticotropin(ACTH)and cortisol(CORT),contents of vasopressin(AVP)and adrenocorticotropin releasing factor(CRH)in the hypothalamus,contents of vasopressin V2 receptor(V2R),glucocorticoid receptor-α(GCR-α),fire channel protein 2(AQP2),cyclic adenosine phosphate(cAMP),protein kinase A(PKA)were determined by Elisa.Renal tissue changes were observed by HE and Masson staining.Results:Compared with model group,high-dose Shenqi Pills group significantly improved body mass(the 21th,28th day),anal temperature(P<0.05,P<0.01),significantly decreased water intake and urine volume(P<0.01),increased hypothalamic CRH,serum ACTH,CORT and urinary 17-OHCS contents(P<0.01),and improved renal injury pathology and renal function indexes.The content of AVP in hypothalamus and the contents of GCR-α,V2R,cAMP,PKA and AQP2 in renal medulla were significantly increased in high-dose Shenqi

关 键 词：水液代谢 肾阳虚 肾气丸 机制 血管加压素-血管加压素V2受体-环磷酸腺苷酸-蛋白激酶A-水通道蛋白2通路 保护作用 腺嘌呤 

分 类 号：R285.5[医药卫生—中药学]