苯磺酸左旋氨氯地平对肾大部切除自发性高血压模型大鼠肾脏的保护作用

Protective Effect of Levamlodipine Besylate on Kidney in Spontaneously Hypertensive Rats After Subtotal Nephrectomy

目的探讨苯磺酸左旋氨氯地平对肾大部(5/6)切除自发性高血压(SH)模型大鼠肾脏的保护作用。方法将40只雄性自发性高血压大鼠随机分为手术组(30只)和假手术组(A组,等体积蒸馏水,10只)。A组剥离肾包膜,暴露肾脏后,关腹。手术组大鼠14 d内行2次手术切除5/6肾脏,术后2周按体质量分层随机分为模型组(B组,等体积蒸馏水,10只)及低、高剂量组[C1组、C2组,2.5,5.0 mg/(kg·d)苯磺酸左旋氨氯地平,各10只]。各组大鼠灌胃给药,每日1次,持续6周。监测大鼠尾动脉收缩压;术中检测大鼠稳定状态下颈动脉血压;采用双缩脲法定量检测大鼠24 h尿蛋白含量;使用全自动生化分析仪检测白细胞介素6(IL-6)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)、超氧化物歧化酶(SOD)、血清肌酐(SCr)、血尿素氮(BUN)水平;观察大体肾脏形态,并采用显微镜观察大鼠肾组织病理形态学变化。结果与A组干预0,1,2,4,6周比较,B组大鼠尾动脉收缩压明显升高(P<0.05);与B组同时点比较,C1组、C2组大鼠尾动脉收缩压明显降低(P<0.05)。与A组干预后比较,B组大鼠颈动脉压及hs-CRP,IL-6,TNF-α,MDA水平均明显升高,SOD,SCr,BUN水平及24 h蛋白定量均明显降低(P<0.05);与B组同时点比较,C1组、C2组大鼠各指标及病理结果均明显改善(P<0.05)。结论苯磺酸左旋氨氯地平对肾大部切除SH模型大鼠的残余肾功能有一定保护作用。

Objective To investigate the protective effect of levamlodipine besylate on the kidney of spontaneous hypertension(SH)rats after 5/6 subtotal nephrectomy.Methods A total of 40 male SH rats were randomly divided into the operation group(30 rats)and sham operation group(group A,equal volume of distilled water,10 rats).The renal capsule of rats in group A was stripped,the kidneys were exposed,and the abdomen was closed.The rats in the operation group were operated twice within 14 d to remove 5/6 kidney,and they were stratified and randomly divided into the model group(group B,equal volume of distilled water,10 rats)and low-dose and high-dose groups[group C1,group C2,2.5,5.0 mg/(kg·d)of levamlodipine besylate,10 rats in each group]according to their body weight at two weeks after the operation.Rats in each group were administered by gavage once a day for six weeks.The systolic blood pressure(SBP)of the rat’s caudal artery was monitored.During the operation,the carotid pressure of rats with steady-state was detected.The 24 h urinary protein quantification of rats was quantitatively detected by the biuret method.The levels of interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP)and tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),superoxide dismutase(SOD),serum creatinine(SCr)and blood urea nitrogen(BUN)were detected by the automatic biochemical analyzer.The gross renal morphology was observed,and the renal histomorphological changes were observed by the microscope.Results The SBP of rat’s caudal artery in group B was significantly higher than that in group A after 0,1,2,4 and 6 weeks of intervention(P<0.05),while that in groups C1 and C2 was significantly lower than that in group B at the same time points(P<0.05).After the intervention,the levels of carotid pressure,hs-CRP,IL-6,TNF-αand MDA in group B were significantly higher than those in group A,while the levels of SOD,SCr,BUN and 24 h urinary protein quantification in group B were significantly lower than those in group A(P<0.05).Compared with group B at the same time points,the indexes and pathological results of rats in groups C1 and C2 were significantly improved(P<0.05).Conclusion Levamlodipine besylate has a certain protective effect on residual renal function in SH rats after subtotal nephrectomy.