槲皮素对脂多糖诱导小鼠急性肾损伤的保护作用及其机制研究

Protective Effects and Mechanism of Quercetin on Lipopolysaccharide-induced Acute Kidney Injury in LPS

目的:探讨槲皮素对脂多糖诱导小鼠急性肾损伤的影响及其机制。方法:18只C57BL/6N小鼠随机分为正常对照组(Control组)、脂多糖诱导的急性肾损伤模型组(LPS组)、槲皮素治疗组(QR组)。脲酶法和肌氨酸氧化酶法分别检测各组小鼠血清中尿素氮和肌酐水平;酶联免疫吸附测定法(ELISA)测定各组小鼠血清中白细胞介素(IL)-1β和白细胞介素(IL)-6水平;原位末端转移酶标记技术(TUNEL)检测各组小鼠肾脏细胞的凋亡;免疫组织化学染色检测各组小鼠肾脏组织中Bax、Bcl-2的表达。结果:与Control组比较,LPS组IL-1β和IL-6水平均升高(P<0.01),肾脏细胞凋亡指数上升(P<0.01),Bax表达增强(P<0.01),Bcl-2表达减弱(P<0.01),Bcl-2/Bax比值降低(P<0.01);与LPS组比较,QR组IL-1β和IL-6水平均下降(P<0.01),肾脏细胞凋亡指数降低(P<0.01),Bax表达减弱(P<0.01),Bcl-2表达增强(P<0.05),Bcl-2/Bax比值升高(P<0.01)。结论:槲皮素可通过上调Bcl-2和下调Bax的表达,抑制肾损伤小鼠肾脏细胞凋亡,并降低炎性因子IL-1β和IL-6的释放,发挥其对LPS诱导小鼠急性肾损伤的保护作用。

Objective To investigate the effect and mechanism of quercetin on lipopolysaccharide(LPS)-induced acute kidney injury in mice.Methods A total of 18 C57 BL/6 N mice were randomly divided into three groups:normal control group(Control group),LPS-induced acute kidney injury model group(LPS group)and quercetin treatment group(QR group),with 6 mice in each group.The serum levels of urea nitrogen and creatinine were respectively detected by urease method and creatinine oxidase method.The serum levels of interleukin(IL)-1βand interleukin(IL)-6 were measured by enzyme-linked immunosorbent assay(ELISA).Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL)was used to detect the apoptosis of renal cells in each group.Immunohistochemical staining was used to detect the expression of Bax and Bcl-2 in kidney tissues of mice in each group.Results Compared with the control group,the serum levels of IL-1βand IL-6 increased(P<0.01),the apoptosis index increased(P<0.01),the expression of Bax increased(P<0.01),the expression of Bcl-2 decreased(P<0.01),and the ratio of Bcl-2/Bax decreased in the LPS group(P<0.01).Compared with the LPS group,the serum levels of IL-1βand IL-6 reduced(P<0.01),the apoptosis index decreased(P<0.01),the expression of Bax decreased(P<0.01),the expression of Bcl-2 increased(P<0.05),and the ratio of Bcl-2/Bax increased in the QR group(P<0.01).Conclusion Quercetin can inhibit renal cell apoptosis through up-regulating Bcl-2 expression and down-regulating Bax expression in LPS-stimulated Mice and reduce the release of inflammation cytokines IL-1βand IL-6,thereby exerting its protective effect on LPS-induced acute renal injury in mice.