在补脾益气法调节PKB/GSK-3β信号通路缓解糖尿病脑病中沉默LncRNA MALAT1的研究  

Study on Tonifying Spleen and Replenishing Qi to Regulate PKB/GSK-3β Signaling Pathway and Silence LncRNA MALAT1 in Diabetic Encephalopathy

作　　者：冯晓帆[1] 王艳杰[1] 刘羽茜 王靖宇 柳春[1] FENG Xiao-fan;WANG Yan-jie;LIU Yu-xi;WANG Jing-yu;LIU Chun(Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning,100847,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《时珍国医国药》2022年第7期1597-1601,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81774022);辽宁省自然科学基金(2019-ZD-0954)。

摘　　要：目的 探讨归脾汤对糖尿病脑病作用的分子机制及沉默LncRNA MALAT1后产生的影响。方法 通过长期高脂饲料喂养及STZ注射建立并筛选糖尿病脑病大鼠模型;应用氧化酶法测大鼠血糖值,ELISA法检测胰岛素水平并计算胰岛素敏感指数,RT-PCR法检测各组大鼠海马中GSK-3β和PKBβmRNA相对表达;应用Western Blot法检测各组大鼠海马组织中GSK-3β、PKB和APP蛋白的相对表达。结果 在药物治疗4周后检测各组大鼠的指标,与模型组比较,M归脾汤组、归脾汤组和西药组大鼠的血糖水平显著降低(P<0.05)、胰岛素敏感指数明显升高(P<0.05);与归脾汤组比较,M归脾汤组大鼠血糖水平显著降低(P<0.05)、胰岛素敏感指数明显升高(P<0.05)。以上结果说明归脾汤在降低糖尿病脑病大鼠血糖水平方面有积极作用,并且能够使沉默LncRNA MALAT1的糖尿病脑病大鼠进一步降低血糖水平。与模型组比较,M归脾汤组、归脾汤组和西药组大鼠海马组织中的GSK-3βmRNA的相对表达显著降低(P<0.05)、PKBβmRNA的相对表达明显升高(P<0.05);与归脾汤组比较,M归脾汤组大鼠海马组织中的GSK-3βmRNA的相对表达显著降低(P<0.05)、PKBβmRNA的相对表达明显升高(P<0.05)。以上结果说明归脾汤在降低糖尿病脑病大鼠海马组织中GSK-3β的mRNA表达方面有积极作用。与模型组比较,M归脾汤组、归脾汤组和西药组大鼠海马组织中的GSK-3β蛋白的相对表达显著降低(P<0.05)、PKB蛋白的相对表达明显升高(P<0.05)、APP蛋白的相对表达显著降低(P<0.05)。与归脾汤组比较,M归脾汤组大鼠海马组织中的APP蛋白的相对表达显著降低(P<0.05)。结论 归脾汤能够缓解糖尿病脑病大鼠模型的胰岛素抵抗情况,这种作用可能是通过调节PKB/GSK-3β信号通路来实现的,并且在沉默大鼠的LncRNA MALAT1后能够使归脾汤的作用效果进一步加强,可为临床上缓解糖尿病脑病提供新的思路。Objective This article discusses the molecular mechanism of Guipi Decoction on diabetic encephalopathy and its effect after silencing LncRNA MALAT1.Methods The rat models of diabetic encephalopathy were established and screened by long-term high-fat diet feeding and STZ injection.Blood glucose was measured by oxidase method,insulin level was detected by ELISA and insulin sensitivity index was calculated.The relative expression of GSK-3β and PKBβ mRNA in hippocampus was detected by RT-PCR;The relative expressions of GSK-3β,PKB and app proteins in hippocampus of rats in each group were detected by Western blot.Results After 4 weeks of drug treatment,the indexes of rats in each group were measured.Compared with the model group,the blood glucose level of rats in M Guipi Decoction group,Guipi Decoction group and Western medicine group decreased significantly(P<0.05),and the insulin sensitivity index increased significantly(P<0.05);Compared with Guipi Decoction group,the blood glucose level of rats in M Guipi Decoction group decreased significantly(P<0.05) and the insulin sensitivity index increased significantly(P<0.05).The above results indicate that Guipi Decoction has a positive effect on reducing blood glucose level in diabetic encephalopathy rats,and can further reduce blood sugar level in diabetic rats with silent LncRNA MALAT1.Compared with the model group,the relative expression of GSK-3β mRNA in hippocampus of M Guipi Decoction group,Guipi Decoction group and Western medicine group decreased significantly(P<0.05),and the relative expression of PKBβ mRNA increased significantly(P<0.05);Compared with Guipi Decoction group,the relative expression of GSK-3β mRNA in hippocampus of M Guipi Decoction group decreased significantly(P<0.05),and the relative expression of PKBβ mRNA increased significantly(P<0.05).These results suggest that Guipi Decoction has a positive effect on reducing the expression of GSK-3β mRNA in hippocampus of diabetic encephalopathy rats.Compared with the model group,the relative expre

关 键 词：糖尿病脑病 归脾汤 肺腺癌转移相关转录本1 GSK-3Β PKB 

分 类 号：R285.5[医药卫生—中药学]