钩藤碱对阿霉素诱导的大鼠肾损伤的作用及其机制

Effects of rhynchophylline on adriamycin-induced renal injury in rats

目的:探讨钩藤碱(rhynchophylline,RHL)对阿霉素致大鼠肾功能损伤的作用及其机制。方法:将52只雌性SD大鼠随机分为生理盐水组(NSG,n=10)、模型组(MG,n=14)、钩藤碱低剂量治疗组(RHL-LG,n=14)和高剂量治疗组(RHL-HG,n=14)。后3组经尾静脉注射阿霉素(5 mg.kg-1)建立肾病模型,NSG注射等容量生理盐水(NS);2周后,RHL-LG和RHL-HG分别给予腹腔注射RHL 5mg.kg-1和15mg.kg-1,NSG和MG分别给予等容量NS。8周后采集血、尿及肾组织标本,检测尿蛋白、血尿素氮(BUN)、血清肌酐(SCr)、组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,进行肾组织病理学观察,RT-PCR检测肾组织中血管紧张素Ⅱ受体1、2(AT1,2-R)、血管紧张素转换酶(ACE)及血管紧张素原(AGT)mRNA的表达。结果:MG的蛋白尿、BUN、SCr和MDA含量明显高于NSG、RHL-LG和RHL-HG(P<0.05),而以RHL-HG的BUN、SCr和MDA含量降低得最为明显;RHL-HG的SOD活性明显高于RHL-LG和MG(P<0.05);MG肾组织病理损伤严重,而RHL-LG和RHL-HG损伤程度明显减轻,RHL-HG轻于RHL-LG;MG肾组织中的AT1-R、ACE和AGT mRNA表达均显著高于RHL-LG,而RHL-LG显著高于RHL-HG(P<0.05),MG AT2-R mRNA表达显著低于RHL-LG,RHL-LG则显著低于RHL-HG(P<0.05)。结论:RHL能减缓阿霉素所致的大鼠肾功能损伤,其机制可能与其减轻肾脏脂质过氧化损伤,调控肾组织中AT1,2-R、ACE和AGT mRNA的表达,增加肾血流量等因素有关。

AIM： To explore the effects of rhynchophylline （RHL） on rat renal injury induced by adriamycin. METHODS： Fifty-two female SD rats were randomly divided into normal saline group （NSG, n = 10）, model group （ MG, n = 14）, low - dose RHL treatment group （ RHL - LG, n = 14） and high - dose RHL treatment group （ RHL - HG, n = 14）. The animals in the latter 3 groups were injected with adriamycin at a dose of 5 mg/kg through the tail vein. The animals in RHL -LG and RHL -HG were treated with RHL at doses of 5 mg/kg and 15 mg/kg, respectively, by intraperitoneal injection for 8 weeks. The animals in NSG and MG were treated with normal saline only. Urine and blood samples were collected to detect the urine protein, blood urea nitrogen （BUN） and serum creatinine （SCr）. The renal tissues of the animals were collected for detection of malondialdehyde （MDA） content, superoxide dismutase （SOD） activity, pathological changes and mRNA expression of angiotension II receptors 1,2 （ AT1,2 - R）, angiotensin - converting enzyme （ACE） and angiotensinogen （AGT）. RESULTS： The urine protein, BUN and SCr in RHL - LG were significantly lower than those in MG, but higher than those in RHL - HG （P 〈 0. 05 ）. The SOD activity in MG was significantly lower than that in RHL - LG in the renal tissues. The SOD activity in RHL - LG was significantly lower than that in RHL - FIG （ P 〈 0. 05 ）, but the content of MDA was on the contrary. The renal pathological damages in RHL - LG were weaker than that in MG, and that in RHL - HG were weaker than that in RHL - LG. The mRNA expression of ATI - R, ACE and AGT in MG was significantly higher than that in RHL - LG in the renal tissues, and that in RHL - LG was higher than that in RHL - HG （ P 〈 0. 05）. The mRNA expression of AT2 - R in MG was significantly lower than that in RHL - LG, and that in RHL - LG was significantly lower than that in RHL - HG （ P 〈 0. 05）. CONCLUSION ： RHL reduces adriamycin - induced renal injury in rats by attenuating the injury of lipid peroxidation in renal tissue, regulating the mRNA expression of ATL 2 -R, ACE and AGT, and increasing renal blood flow.