Zhou L, Liu D W, Zhang F F, Liu S Y, Wang F, Liu Z S, Zhao Q
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.
Zhonghua Yi Xue Za Zhi. 2021 Mar 16;101(10):727-731. doi: 10.3760/cma.j.cn112137-20210120-00184.
To explore the effects and mechanisms of Xuezhikang on preventing contrast-induced nephropathy (CIN) in diabetic rats. 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. 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 <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 <0.05]. Meanwhile, Xuezhikang pretreatment downregulated the mRNA and protein expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (both <0.05). The current study suggests that Xuezhikang protects against CIN in diabetic rats by inhibiting oxidative stress and inflammation.
探讨血脂康预防糖尿病大鼠造影剂肾病(CIN)的作用及机制。腹腔注射链脲佐菌素(65mg/kg),在7周龄雄性Sprague-Dawley(SD)大鼠中建立糖尿病模型。造模4周后,将24只糖尿病大鼠随机分为4组:假手术组、CIN组、CIN+溶媒(Veh)组和血脂康组。造影剂给药24小时后处死所有动物。采集血液和肾脏组织,检测生化、炎症相关、氧化应激相关及病理指标。造影剂给药后,血脂康组肾功能相关指标较CIN+Veh组降低[血清肌酐(SCr):(59.3±3.3)μmol/L对(73.2±4.1)μmol/L;血尿素氮(BUN):(13.8±0.5)mmol/L对(16.3±0.6)mmol/L;血清中性粒细胞明胶酶相关脂质运载蛋白(sNGAL):(41.4±2.0)ng/ml对(54.9±4.4)ng/ml;尿肾损伤分子-1(uKIM-1):(11.1±0.5)ng/ml对(16.6±0.5)ng/ml](均<0.05)。组织学分析显示,血脂康组肾小管扩张、刷状缘丧失及肾小管细胞坏死的严重程度优于CIN+Veh组。此外,血脂康组氧化应激相关指标较CIN+Veh组改善[丙二醛(MDA):(12.1±0.7)nmol/mg对(15.5±0.8)nmol/mg,超氧化物歧化酶(SOD):(35.0±2.2)U/mg对(23.7±3.4)U/mg,肾亚硝酸盐:(1.7±0.1)nmol/mg对(1.2±0.1)nmol/mg,均<0.05]。同时,血脂康预处理下调肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-)的mRNA和蛋白表达(均<0.05)。本研究提示,血脂康通过抑制氧化应激和炎症反应对糖尿病大鼠CIN具有保护作用。