盐酸西那卡塞调节PI3K/Akt/FoxO1信号通路在糖尿病大鼠的作用机制研究

Study on the mechanism of cinacaset hydrochloride regulating PI3K/Akt/FoxO1 signal pathway in diabetes rats

目的探讨盐酸西那卡塞调节磷脂酰肌醇-3-激酶(PI3K)/丝苏氨酸蛋白激酶(Akt)/叉头框转录因子O1(FoxO1)信号通路在糖尿病大鼠的作用机制。方法共60只Wistar大鼠中,随机选取15只将其设为对照组,其余45只建立糖尿病模型(经腹腔注射链脲佐菌素)成功后,按照随机数字表法依次设为模型组(n=15)、盐酸二甲双胍组(n=15)、盐酸西那卡塞组(n=15)。对照组、模型组给予0.9%氯化钠溶液灌胃,盐酸二甲双胍组给予盐酸二甲双胍干预,盐酸西那卡塞组给予盐酸西那卡塞干预。比较各组大鼠血糖指标[空腹血糖、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)]、血脂指标[总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、肾功能指标[血肌酐、尿素氮、24 h尿微量白蛋白]、甲状腺功能[甲状旁腺激素(PTH)、甲状腺体积]及PI3K/Akt/FoxO1表达。结果与对照组比较,盐酸二甲双胍组、盐酸西那卡塞组、模型组的空腹血糖、HbA1c、FINS、总胆固醇、甘油三酯、LDL-C水平逐渐上升,而HDL-C水平逐渐下降,差异均有统计学意义(P<0.05)。与对照组比较,盐酸西那卡塞组、盐酸二甲双胍组、模型组的血肌酐、尿素氮、24 h尿微量白蛋白水平依次升高,差异均有统计学意义(P<0.05)。与对照组比较,盐酸西那卡塞组、盐酸二甲双胍组、模型组的PTH水平依次升高,甲状腺体积依次增大,差异均有统计学意义(P<0.05)。与对照组比较,盐酸西那卡塞组、盐酸二甲双胍组、模型组的PI3K、Akt、FoxO1表达水平依次降低,差异均有统计学意义(P<0.05)。结论盐酸西那卡塞能够有效调节糖尿病大鼠的血糖、血脂指标,改善肾功能和甲状腺功能,调控PI3K/Akt/FoxO1信号通路可能是其发挥作用的重要机制。

Objective To explore the mechanism of Sinacathe hydrochloride regulating phosphatei-dylinositol 3 kinase(PI3K)/serine-threonine kinase(Akt)/fork head box O1(FoxO1)signaling pathway in diabetes rats.Methods Fifteen Wistar rats were randomly selected from 60 Wistar rats,and they were set as the control group.After the establishment of the diabetes model(intraperitoneal injection of streptozotocin)in the remaining 45 rats was successful,they were successively set as the model group(n=15),metformin hydrochloride group(n=15),and sinecase hydrochloride group(n=15)according to the random number table method to carry out prospective research.The control group and model group were given normal saline by gavage,the metformin hydrochloride group was given metformin hydrochloride intervention,and the sinacase hydrochloride group was given sinacase hydrochloride intervention.The blood glucose indicators[fasting blood glucose,hemoglobin A1c(HbA1c),fasting insulin(FINS)],blood lipid indicators[total cholesterol,triglycerides,low-density lipoprotein cholesterol(LDL-C)levels,high-density lipoprotein cholesterol(HDL-C)],renal function indicators(blood creatinine,urea nitrogen,24-hour urinary microalbumin),thyroid function[parathyroid hormone(PTH),thyroid volume]and PI3K/Akt/FoxO1 expression were compared.Results Compared with the control group,the metformin hydrochloride group,and the sinakase hydrochloride group,the model group,the levels of FBG,HbA1c,FINS,total cholesterol,triglyceride,LDL-C gradually increased,while the level of HDL-C gradually decreased,the differences were statistically significant(P<0.05).Compared with the control group,the levels of serum creatinine,urea nitroge,and 24-hour urine microalbumin in the senecase hydrochloride group,metformin hydrochloride group,and model group increased in turn,the differences were statistically significant(P<0.05).Compared with the control group,the levels of PTH and thyroid volume in the senecase hydrochloride group,metformin hydrochloride group and model group gradually increased,the differences were statistically significant(P<0.05).Compared with the control group,the expression levels of PI3K,Akt and FoxO1 in the senecase hydrochloride group,metformin hydrochloride group and model group were gradually decreased,the differences were statistically significant(P<0.05).Conclusion Sinarcet hydrochloride can effectively regulate blood glucose and lipid indicators in diabetes rats,improve renal function and thyroid function,and regulate PI3K/Akt/FoxO1 signaling pathway may be an important mechanism of its role.