黄连素对高脂饲料联合链脲佐菌素诱导2型糖尿病大鼠T细胞亚群及炎症因子的影响

Effects of berberine on T cell subsets and inflammatory factors in type 2 diabetic rats induced by high-fat diet combined with streptozotocin

目的探讨黄连素对高脂饲料联合链脲佐菌素诱导2型糖尿病大鼠T细胞亚群及炎症因子的影响。方法以高脂饲料联合链脲佐菌素诱导SD大鼠复制2型糖尿病模型,将造模成功的40只大鼠随机分为模型组、二甲双胍组、黄连素高剂量(300 mg/kg)组、黄连素低剂量(150 mg/kg)组各10只,另取10只正常SD大鼠作为正常组。造模后,二甲双胍组灌胃200 mg/kg二甲双胍,黄连素高、低剂量组分别灌胃300 mg/kg和150 mg/kg黄连素,正常组和模型组灌胃等体积的生理盐水,均连续2周。末次灌胃后12 h,采集各组大鼠腹主动脉血,检测空腹血糖(FPG)、总胆固醇(TC)、三酰甘油(TG)、炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、干扰素-γ(IFN-γ)]及T淋巴细胞(CD4+、CD8+)表达水平;取大鼠脾脏组织,采用Western blot法检测CD4+、CD8+表达水平。结果与正常组比较,模型组大鼠血清中FPG、TC、TG、TNF-α、IL-1β、IFN-γ水平及CD8+比例和脾脏组织中CD8+表达水平均显著升高,血清中CD4+比例、CD4+/CD8+比值和脾脏组织中CD4+表达水平均显著降低,差异均有统计学意义(P均<0.05);与模型组比较,二甲双胍组和黄连素高、低剂量组大鼠血清中FPG、TC、TG、TNF-α、IL-1β、IFN-γ水平及CD8+比例和脾脏组织中CD8+表达水平均显著降低,血清中CD4+比例、CD4+/CD8+比值和脾脏组织中CD4+表达水平均显著升高,差异均有统计学意义(P均<0.05),二甲双胍组和黄连素高、低剂量组各指标比较差异均无统计学意义(P均>0.05)。结论黄连素可降低高脂饲料联合链脲佐菌素诱导的2型糖尿病大鼠血糖和血脂水平,其作用机制可能与调控炎症因子及T细胞水平有关。

Objective It is to investigate the effect of berberine on T cell subsets and inflammatory factors in type 2 diabetic rats induced by high-fat diet combined with streptozotocin.Methods SD rats were induced to replicate type 2 diabetes models with high-fat diet combined with streptozotocin.40 successfully modeled rats were randomly divided into model group,metformin group,and high dose berberine(300 mg/kg)group,low dose berberine(150 mg/kg)group,10 rats in each group,and another 10 normal SD rats were selected as the normal group.After modeling,the metformin group was given 200 mg/kg metformin by gavage,the high dose berberine group and low dose berberine group were given 300 mg/kg and 150 mg/kg of berberine respectively by gavage,the normal group and the model group were given equal volumes of normal saline by gavage.All the groups were treated for 2 weeks.At 12h after the last gavage,the blood was collected from the abdominal aorta of rats in each group to detect the levels of fasting blood glucose(FPG),total cholesterol(TC),triacylglycerol(TG),inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)]and T lymphocytes(CD4+,CD8+);the spleen tissues of the rats were taken to detect the expression levels of CD4+and CD8+by Western blot.Results Compared with the normal group,the serum levels of FPG,TC,TG,TNF-α,IL-1β,IFN-γand the ratio of CD8+and the expression of CD8+in the spleen tissue were significantly increased,while the ratio of CD4+in the serum,CD4+/CD8+ratio and CD4+expression level in spleen tissue were significantly reduced in the model group,and the differences were statistically significant(P<0.05).Compared with the model group,the serum levels of FPG,TC,TG,TNF-α,IL-1β,IFN-γand the ratio of CD8+and the expression of CD8+in the spleen tissue were significantly decreased,while the ratio of CD4+in the serum,CD4+/CD8+ratio and CD4+expression level in spleen tissue were significantly increased in the metformin group,high dose berberine group,low dose berberine group,and the differences were statistically significant(P<0.05).There was no statistically significant difference in these indicators between the metformin group and the berberine groups(all P>0.05).Conclusion Berberine can reduce the levels of blood glucose and blood lipid in type 2 diabetic rats induced by high-fat diet combined with streptozotocin,and its mechanism may be related to the regulation of inflammatory factors and T cell levels.