摘要
目的 探讨肠道微生物群移植(FMT)和益生菌补充剂对妊娠期糖尿病(GDM)大鼠抗炎症、抗氧化及妊娠结局的影响,为临床应用提供基础依据.方法 取50只SD雌性大鼠和25只SD雄性大鼠,2∶1合笼,交配成功后随机抽取10只雌鼠为对照组,其余雌鼠腹腔注射链脲佐菌素建立GDM大鼠模型,随机分为模型组、益生菌组、FMT组、FMT+益生菌组,每组10只.FMT组给予10mL/kg粪便混悬液灌胃,益生菌组给予359.708 mg/kg益生菌制剂灌胃,FMT+益生菌组给予10mL/kg粪便混悬液和359.708 mg/kg益生菌制剂灌胃,模型组、对照组进行等量PBS缓冲液灌胃,每天一次,14d后检测大鼠血清中空腹血糖(FBG)、空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素6(IL-6)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)水平,记录大鼠的胎鼠体重、胎盘重量及胎鼠存活数.结果 模型组大鼠的胎鼠体重、胎盘重量,血清中FBG、TC、TG、LDL、FINS、TNF-α、IL-1β、IL-6水平,肠道菌群弯曲菌门、脱硫杆菌门相对丰度均显著高于对照组(均P＜0.05);模型组大鼠活胎鼠数量,血清中 HDL 水平,SOD、GSH-Px 活性,肠道菌群 Ace 指数、Chao1 指数,LachnospiraceaeNK4A136 group、未分类毛螺菌属相对丰度均显著低于对照组(均P＜0.05);FMT组、益生菌组、FMT+益生菌组大鼠的胎鼠体重、胎盘重量,血清中FBG、TC、TG、LDL、FINS、TNF-α、IL-1β、IL-6水平均显著低于模型组(均P＜0.05);FMT组、FMT+益生菌组大鼠肠道菌群Ace指数、Chao1指数及弯曲菌门相对丰度均显著高于模型组(均P＜0.05);益生菌组Ace指数、Chao1指数均显著低于对照组(均P＜0.05),拟杆菌门、放线菌门、LachnospiraceaeNK4A136 group相对丰度均显著高于模型组(均P＜0.05),厚壁菌门相对丰度显著低于模型组(P＜0.05);FMT组、益生菌组、FMT+益生菌联合组大鼠活胎鼠数量,血清中HDL水平,SOD、GSH-Px活性均显著高于模型组(均P＜0.05).结论 FMT和益生菌补充剂可以减轻GDM大鼠炎症程度,改善氧化应激损伤,改变大鼠妊娠结局.
Abstract
Objective To observe the effects of fecal microbiota transplantation(FMT)and probiotic supplementation on anti-inflammation,antioxidant activity and pregnancy outcomes in gestational diabetes mellitus(GDM)rats.Methods Fifty female SD rats and twenty-five male ones were paired in a 2∶1 ratio.After successful mating,ten female rats were randomly selected as the control group.The remaining female rats were intraperitoneally injected with STZ to es-tablish the GDM rat models,and were randomly divided into the model group,probiotic group,FMT group,and combina-tion of FMT and probiotic group.The FMT group received 10 mL/kg of fecal suspension by gavage,the probiotic group was given 359.708 mg/kg of probiotic formulation,while the combination group received both 10 mL/kg of fecal suspen-sion and 359.708 mg/kg of probiotic formulation.The model and control groups were given an equivalent volume of PBS buffer.Each treatment was administered once daily for 14 days.Afterward,serum levels of fasting blood glucose(FBG),fasting insulin(FINS),total cholesterol(TC),triglycerides(TG),low-density lipoprotein(LDL),high-density lipoprotein(HDL),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were measured.The weight of rat placenta,number of sur-vival fetuses and their weights were also recorded.Results In the model group,the weights of fetuses and placentas,and the levels of FBG,TC,TG,LDL,FINS,TNF-α,IL-1β and IL-6 in serum,as well as the relative abundances of Bacteroid-etes and Desulfovibrionaceae in intestinal flora were significantly higher,while the number of survival fetuses,serum HDL level,activities of SOD and GSH-Px,Ace index,Chao1 index,and abundances of Lachnospiraceae NK4A136 group andunclassified Clostridiaceae abundance in intestinal flora were significantly lower than those in the control group,respect-ively(all P＜0.05).In the FMT group,probiotic group and combination group,the weights of fetuses and placentas,and the levels of FBG,TC,TG,LDL,FINS,TNF-α,IL-1β and IL-6 in serum were significantly lower than those in the model group respectively(all P＜0.05).In the FMT group and combination group,the Ace index,Chao1 index and Bacteroidetes abundance were significantly higher than those in the model group respectively(all P＜0.05).In the probiotic group,the Ace index and Chao1 index were significantly lower than those in the control group respectively(all P＜0.05);the abund-ances of Bacteroidetes,Actinobacteria and Lachnospiraceae NK4A136 group were significantly higher,while that of Firmi-cutes was significantly lower than in the model group,respectively(all P＜0.05).In the FMT group,probiotic group and combination group,the numbers of survival fetuses,serum HDL levels,and activities of SOD and GSH-Px were higher than those in the model group,respectively(all P＜0.05).Conclusion FMT and probiotic supplementation can alleviate the degree of inflammation in GDM rats,improve oxidative stress damage,and modify pregnancy outcomes in rats.
基金项目
新疆维吾尔自治区自然科学基金(2022D01C444)
NETL
NSTL
万方数据