小檗碱对代谢综合征肾损害CHOP mRNA、GRP78 mRNA和炎症因子的影响

Effect of Berberine on expression of CHOP mRNA,GRP78 mRNA and inflammatory cytokines in patients with metabolic syndrome and renal damage

目的:观察小檗碱对代谢综合征合并肾损害患者C/EBP同源蛋白(C/EBP homology protein,CHOP)mRNA、糖调节蛋白78(glucose-regulated protein 78,GRP78)mRNA表达和炎症因子的影响,探讨小檗碱对保护代谢综合征合并肾损害的分子生物学机制。方法:收集2015年2月至2015年12月福州总医院肾内科临床诊断符合代谢综合征合并肾损害的患者20例,随机分为治疗组10例(给予盐酸小檗碱300 mg,3次/d);对照组10例(采用常规西药治疗)。疗程8周,观察两组治疗前、治疗4周、8周后尿微量白蛋白/肌酐比值(U-m Alb/C)、血清肌酐(SCr)及尿素氮(BUN)的变化。采用RT-PCR法检测尿液中CHOP mRNA、GRP78 mRNA的表达;采用ELISA法检测血清中白细胞介素8(IL-8)、肿瘤坏死因子α(TNF-α)的含量。结果:治疗8周后,对照组和治疗组尿微量白蛋白/肌酐比值分别较治疗前下降(P<0.05)。与对照组比较,治疗组尿微量白蛋白/肌酐比值下降更明显(P<0.05)。两组治疗前后SCr及BUN水平无显著性差异。治疗8周后,治疗组尿液CHOP mRNA、GRP78 mRNA的表达及血清IL-8、TNF-α的含量均较治疗前显著降低(P<0.05),对照组治疗前后差异无统计学意义;与对照组比较,治疗组尿液CHOP mRNA、GRP78 mRNA的表达及血清IL-8、TNF-α的含量均下降更明显(P<0.05)。结论:小檗碱可减少代谢综合征合并肾损害患者的白蛋白尿,降低肾脏组织过度激活的内质网应激反应,改善炎症状态。

Objective： To investigate the effects of berberine（ BBR） on the expression of CHOP mRNA,GRP78 mRNA and inflammatory cytokines in patients with metabolic syndrome complicated with renal damage,and to explore the molecular mechanism of BBR in the metabolic syndrome with renal damage. Methodology： Twenty patients with metabolic syndrome complicated with renal damage were enrolled into this study. They were randomly divided into treatment group of 10 cases were given berberine 300 mg,3 times/day,and other 10 cases in control group were treated by routine medicine. The therapeutic course for both groups was 8 weeks. The indexes of efficacy including microalbumin/creatinine ratio（ U-m Alb/C）,serum creatinine（ SCr） and urea nitrogen（ BUN） were observed. RT-PCR was used to detect the expression of CHOP mRNA and GRP78 mRNA in urine,and the content of interleukin（ IL）-8 and tumor necrosis factor（ TNF）-alpha in serum were detected by ELISA. Results： After treatment for 8 weeks,the U-m Alb/C in the control group and the treatment group was lower than that before treatment（ P〈0. 05）. Compared with the control group,the Um Alb/C in the treatment group was decreased more significantly（ P0. 05）. There was no significant difference between the two groups before and after treatment of SCr and BUN（ P〉0. 05）. After 8 weeks of treatment,Urine CHOP mRNA,GRP78 mRNA expression and the contentof serum IL-8 and TNF-α in the treatment group were significantly lower than that before treatment,the difference was statistically significant（ P〈0. 05）,the control group before and after treatment there was no statistically significant difference（ P〈0. 05）. Compared with control group,urine CHOP mRNA,GRP78 mRNA expression and the content of serum IL-8 and TNF-α in treatment group was decreased obviously（ P〈0. 05）.Conclusion： Berberine can reduce albuminuria in patients with metabolic syndrome and renal damage,its molecular mechanism may be related to reduce the excessive activation of endoplasmic reticulum stress response and improve the state of inflammation.