四君子汤对2型糖尿病小鼠肠屏障的影响

Effect of Sijunzi Decoction on intestinal barrier of type 2 diabetic mice

探讨四君子汤对糖尿病小鼠肠屏障的改善作用。C57BL/6J小鼠给予高糖高脂饲料联合链脲佐菌素(STZ)建立2型糖尿病(T2DM)模型。将T2DM小鼠随机分为空白组、T2DM组、多奈哌齐(DON)组、罗格列酮(RGZ)组、四君子汤不同剂量(7.5、15、30 g·kg^(-1))组,灌胃给药6周。记录小鼠体质量和空腹血糖(FBG);测定空腹血清胰岛素(FINS)和胰岛素抵抗指数(HOMA-IR),观察胰岛素抵抗(IR)作用;分析肠道菌群及血清中5-羟色胺(5-HT)、内毒素(LPS)、短链脂肪酸(SCFAs)水平;通过HE染色与免疫组化观察小鼠结肠结构和紧密连接蛋白occludin、claudin-1、ZO-1的变化;自发交替实验观察空间记忆能力。与空白组比较,T2DM组小鼠FBG、HOMA-IR显著增加(P<0.01);物种丰度指数(Sobs指数)、香农多样性指数(Shannon指数)、物种丰度估计指数(Chao指数)降低;LPS显著增加(P<0.001),5-HT、SCFAs、occludin、claudin-1、ZO-1水平显著降低(P<0.01),结肠屏障功能受损;自发交替正确率显著降低(P<0.05)。四君子汤治疗6周后,与T2DM组相比,四君子汤15 g·kg^(-1)组小鼠FBG、HOMA-IR显著降低(P<0.01);Sobs指数、Shannon指数、Chao指数升高;LPS显著降低(P<0.01),5-HT、SCFAs、occludin、claudin-1、ZO-1水平显著升高(P<0.05),结肠屏障功能改善;自发交替正确率显著升高(P<0.001)。综上,四君子汤具有改善糖尿病小鼠肠屏障的作用。

This study aims to explore the improvement effect of Sijunzi Decoction on intestinal barrier in diabetic mice.A type 2 diabetes mellitus(T2DM)model was established in C57BL/6J mice by feeding them with high-sugar and high-fat diet combined with streptozotocin(STZ).The T2DM mice were randomly divided into a control group,a T2DM group,a donepezil(DON)group,a rosiglitazone(RGZ)group,and Sijunzi Decoction groups(7.5,15,and 30 g·kg^(-1)),and orally administered for six weeks.The body weight and fasting plasma glucose(FBG)of mice were recorded.Fasting plasma insulin(FINS)and insulin resistance index(HOMA-IR)were observed to assess insulin resistance(IR).Intestinal flora and levels of serotonin(5-HT),lipopolysaccharide(LPS),and short-chain fatty acids(SCFAs)in serum were analyzed.Changes in colonic structure and tight junction proteins occludin,claudin-1,and ZO-1 were observed through HE staining and immunohistochemistry.Spontaneous alternation test was conducted to observe the effect on spatial memory ability.Compared with the results in the control group,FBG and HOMA-IR in the T2DM group were significantly increased(P<0.01);species richness index(Sobs index),Shannon diversity index(Shannon index),and species abundance estimate index(Chao index)were decreased;LPS was significantly increased(P<0.001),while the levels of 5-HT,SCFAs,occludin,claudin-1,and ZO-1 were significantly decreased(P<0.01),indicating impaired colonic barrier function;spontaneous alternation accuracy was significantly decreased(P<0.05).After 6 weeks of Sijunzi Decoction treatment,compared with the results in the T2DM group,FBG and HOMA-IR in the Sijunzi Decoction 15 g·kg^(-1) group were significantly decreased(P<0.01);Sobs index,Shannon index,and Chao index were increased;LPS was significantly decreased(P<0.01),while the levels of 5-HT,SCFAs,occludin,claudin-1,and ZO-1 were significantly increased(P<0.05),indicating improved colonic barrier function;spontaneous alternation accuracy was increased(P<0.001).In conclusion,Sijunzi Decoction has the effect of improving intestinal barrier in diabetic mice.