血脂康预防造影剂所致糖尿病大鼠急性肾损伤机制的实验观察  

Effects and mechanisms of Xuezhikang on preventing contrast-induced acute kidney injury in diabetic rats

作　　者：周炉 刘东伟 张芳菲 刘水英 王锋[1] 刘章锁 赵清[3] Zhou Lu;Liu Dongwei;Zhang Fangfei;Liu Shuiying;Wang Feng;Liu Zhangsuo;Zhao Qing(Department of Nephrology,Shanghai Jiao Tong University Affiliated Sixth People′s Hospital,Shanghai 200233,China;Department of Nephrology,the First Affiliated Hospital of Zhengzhou University/Research Institute of Nephrology,Zhengzhou University,Zhengzhou 450052,China;Department of Cardiology,Shanghai Jiao Tong University Affiliated Sixth People′s Hospital,Shanghai 200233,China)

机构地区：[1]上海交通大学附属第六人民医院肾内科,上海200233 [2]郑州大学第一附属医院肾脏病中心郑州大学肾脏病研究所,郑州450052 [3]上海交通大学附属第六人民医院心内科,上海200233

出　　处：《中华医学杂志》2021年第10期727-731,共5页National Medical Journal of China

基　　金：国家自然科学基金(81700601,81870504);国家科技重大专项项目(2020ZX09201-009);上海市徐汇区卫生健康委员会科研项目(SHXH201605,SHXH201648)。

摘　　要：目的探讨血脂康对糖尿病大鼠造影剂诱导肾损伤的保护作用及相关机制。方法7周龄健康雄性SD大鼠,链脲佐菌素(STZ)腹腔注射(65 mg/kg)建立糖尿病模型。造模4周后,取24只糖尿病大鼠随机分为4组:假手术组、造影剂肾病组、术前生理盐水灌胃的造影剂肾病组(生理盐水组)、术前血脂康灌胃的造影剂肾病组(血脂康组),每组6只。所有动物均于造影剂给药24 h后处死,收集血液和肾脏组织,检测生化、炎症、氧化应激以及病理等相关指标。结果给予造影剂24 h后,与生理盐水组相比,血脂康组大鼠血肌酐[(59.3±3.3)μmol/L比(73.2±4.1)μmol/L]、血尿素氮[(13.8±0.5)mmol/L比(16.3±0.6)mmol/L]、血清中性粒细胞明胶酶相关脂蛋白(sNGAL)[(41.4±2.0)ng/ml比(54.9±4.4)ng/ml]和尿肾损伤分子1(uKIM-1)[(11.1±0.5)ng/ml比(16.6±0.5)ng/ml]均降低(均P<0.05)。与生理盐水组比较,血脂康组肾小管扩张、刷状边界丧失和肾小管细胞坏死的程度较轻。进一步的机制研究结果显示,血脂康组氧化应激指标改善,与生理盐水组比较,血脂康组肾丙二醛[(12.1±0.7)nmol/mg比(15.5±0.8)nmol/mg]降低,超氧化物歧化酶[(35.0±2.2)U/mg比(23.7±3.4)U/mg]和肾亚硝酸盐[(1.7±0.1)nmol/mg比(1.2±0.1)nmol/mg]升高(均P<0.05)。炎症反应水平检测结果显示,与生理盐水组相比,血脂康组肿瘤坏死因子α、白细胞介素6的mRNA和蛋白表达水平均降低(均P<0.05)。结论血脂康可能通过降低氧化应激,抑制炎症反应来减轻糖尿病大鼠造影剂诱导的肾功能不全和组织病理学损伤。Objective To explore the effects and mechanisms of Xuezhikang on preventing contrast-induced nephropathy(CIN)in diabetic rats.Methods Streptozotocin(65 mg/kg)was injected intraperitoneally to establish a diabetes model in 7-week-old male Sprague-Dawley(SD)rats.After 4 weeks of modeling,24 diabetic rats were randomly divided into 4 groups:sham group,CIN group,CIN+vehicle(Veh)group and Xuezhikang group.All animals were sacrificed at 24 hours after administration of contrast.Blood and kidney tissues were collected to detect biochemical,inflammation-related,oxidative stress-related and pathological indicators.Results After administration of contrast agent,the renal function-related indicators were decreased in Xuezhikang group compared with CIN+Veh group[serum creatinine(SCr):(59.3±3.3)μmol/L vs(73.2±4.1)μmol/L;blood urea nitrogen(BUN):(13.8±0.5)mmol/L vs(16.3±0.6)mmol/L;serum neutrophil gelatinase-associated lipocalin(sNGAL):(41.4±2.0)ng/ml vs(54.9±4.4)ng/ml;urinary kidney injury moleculer-1(uKIM-1):(11.1±0.5)ng/ml vs(16.6±0.5)ng/ml](all P<0.05).Histological analysis showed that the severity of renal tubule dilatation,brush border loss and renal tubular cell necrosis in Xuezhikang group was better than that of CIN+Veh group.Additionally,the oxidative stress-related indicators of Xuezhikang group improved compared with those of CIN+Veh group[malondialdehyde(MDA):(12.1±0.7)nmol/mg vs(15.5±0.8)nmol/mg,superoxide dismutase(SOD):(35.0±2.2)U/mg vs(23.7±3.4)U/mg,renal nitrite:(1.7±0.1)nmol/mg vs(1.2±0.1)nmol/mg,all P<0.05].Meanwhile,Xuezhikang pretreatment downregulated the mRNA and protein expression of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)(both P<0.05).Conclusion The current study suggests that Xuezhikang protects against CIN in diabetic rats by inhibiting oxidative stress and inflammation.

关 键 词：糖尿病 造影剂肾病 血脂康 氧化应激 炎症 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]