小檗碱对代谢综合征内质网应激IRE1-XBP1通路的影响

Effects of berberine on IRE1-XBP1 pathway in endoplasmic reticulum stress in metabolic syndrome patients

目的:观察小檗碱对代谢综合征合并肾损害患者尿肌醇酶1(IRE1)、X盒结合蛋白1(XBP1)、半胱天冬酶12(caspase-12)mRNA及血、尿IRE1、XBP1、caspase-12蛋白表达的影响,从内质网应激机制探讨小檗碱对代谢综合征合并肾损害的保护作用。方法:选取2016年2月至2017年1月联勤保障部队第九○○医院临床诊断符合代谢综合征合并肾损害患者20例,随机分成对照组、治疗组,每组各10例,对照组给予基础治疗;治疗组在基础治疗同时,加用小檗碱,疗程8周。同时选取在性别、年龄相匹配的健康人10例为健康组。观察各组的治疗疗效。结果:治疗8周后,治疗组BMI、FBG、2hPBG,TG、LDL-C、FINS水平均低于对照组(P<0.05)。治疗8周后,治疗组尿IRE1、XBP1、caspase-12 mRNA,尿及血IRE1、XBP1、caspase-12蛋白的表达均低于对照组(P<0.05),且随着治疗时间的延长,治疗组尿IRE1、XBP1、caspase-12 mRNA,血及尿IRE1、XBP1、caspase-12蛋白的表达进一步下降(P<0.05),而对照组无明显差异(P>0.05)。结论:小檗碱可改善代谢综合征合并肾损害患者的胰岛素抵抗,调节糖脂代谢紊乱,并减少尿IRE1、XBP1、caspase-12 mRNA,血及尿IRE1、XBP1、caspase-12蛋白的表达,其机制可能与小檗碱可以抑制代谢综合征合并肾损害患者内质网应激IRE1-XBP1通路的过度激活有关。

Objective:To observe the effects of berberine on urinary inositol-requiring enzyme(IRE1),x-box binding protein-1(XBP1),caspase-12 mRNA and the expression of IRE1,XBP1,caspase-12 in blood and urine of patients with metabolic syndrome and renal damage,and to explore the metabolism of berberine from endoplasmic reticulum stress mechanism.Methodology:20 patients with metabolic syndrome and renal damage were randomly divided into control group(n=10),treatment group(n=10).Basic treatments of metabolic syndrome were given to patients in group A.Berberine were prescribed to patients in group B addition to basic treatments.Patients were observed for 8 weeks.At the same time,10 healthy people with gender and age matched were selected as healthy group(n=10).Results:After 8 weeks of treatment,the body mass ind(BMI),FBG,2hPBG,triglyceride(TG),low density lipoprotein chesterol(LDLC),and fasting insulin(FINS)levels in the treatment group were lower than those in the control group(P<0.05),and the treatment group was superior to the control group(P<0.05).After 8 weeks of treatment,the expressions of urinary IRE1,XBP1,caspase-12 mRNA,urine and blood IRE1,XBP1 and caspase-12 protein in the treatment group were lower than those in the control group(P<0.05),and its expression decreased further with the prolongation of treatment time(P<0.05)in treatment group.Conclusion:Berberine can improve insulin resistance,regulate glucose and lipid metabolism disorders in patients with metabolic syndrome conbined with renal damage,and reduce the expression of urinary IRE1,XBP1,caspase-12 mRNA,blood and urine IRE1,XBP1,caspase-12 proteins.The mechanism may be related to berberine inhibiting the excessive activation of the IRE1-XBP1 pathway in endoplasmic reticulum stress.