石榴皮多酚对妊娠糖尿病大鼠炎症反应及TLR4/NF-κB信号通路的影响

Effects of pomegranate peel polyphenols on inflammatory response and TLR4/NF-κB signaling pathway in gestational diabetes mellitus rats

目的探讨石榴皮多酚(PPPs)对妊娠糖尿病(GDM)大鼠肾脏炎症反应及TLR4/NF-κB信号通路的影响。方法通过腹腔注射链脲佐菌素(STZ)建立GDM大鼠模型,将大鼠分为对照组(Control组)、GDM组、PPPs组(300 mg/kg PPPs)、脂多糖(LPS)组(0.1 mg/kg LPS)、PPPs+LPS组(300 mg/kg PPPs+0.1 mg/kg LPS),给药2周后,检测大鼠空腹血糖(FBG)及血脂、肾功能指标;称取胎鼠体质量及胎盘质量;检测肾脏组织炎症因子水平;H-E染色观察肾脏病理变化;Westernblot检测肾脏组织TLR4、p-NF-κBp65、p-IκB-α蛋白表达。结果GDM组大鼠FBG、血脂指标(TC、TG、LDL)、肾功能指标(UA、BUN、Cr)、肾脏组织炎症因子(TNF-α、IL-1β、IL-6)水平与肾组织TLR4、p-NF-κB p65、p-IκB-α蛋白表达水平较Control组显著升高(P<0.05),肾脏组织发生病理损伤,胎鼠体质量及胎盘质量亦显著高于Control组(P<0.05);PPPs可显著降低GDM大鼠FBG、血脂和肾功能指标、肾脏组织炎症因子水平和肾组织TLR4、p-NF-κB p65、p-IκB-α蛋白表达水平(P<0.05),降低胎鼠体质量及胎盘质量(P<0.05),减轻肾脏组织病理损伤;此外,LPS对GDM大鼠的作用效果与PPPs相反,且PPPs对GDM大鼠的作用可被LPS逆转。结论PPPs可通过抑制TLR4/NF-κB信号通路,改善GDM大鼠糖脂代谢紊乱与炎症反应,保护肾脏损伤。

Objective To investigate the effects of pomegranate peel polyphenols(PPPs)on renal inflammation and TLR4/NF-κB signaling pathway in gestational diabetes mellitus(GDM)rats.Methods GDM rat models were established by intraperitoneal injection of streptozotocin(STZ).The rats were divided into Control group,GDM group,PPPs group(300mg/kg PPPs),lipopolysaccharide(LPS)group(0.1 mg/kg LPS),PPPs+LPS group(300 mg/kg PPPs+0.1 mg/kg LPS).After 2weeks of administration,the rats were tested for fasting blood glucose(FBG),blood lipids,and renal function indexes.The weight of the fetal rats and the weight of the placenta were weighed.The level of inflammatory factors in kidney tissue was detected.The pathological changes of the kidney were observed by H-E staining,and the expression of TLR4,p-NF-κB p65,and p-IκB-αproteins in kidney tissue was detected by Western blot.Results In the GDM group,the FBG,blood lipid indexes(TC,TG,LDL),renal function indexes(UA,BUN,Cr),renal tissue inflammatory factors(TNF-α,IL-1β,IL-6)levels and renal tissue TLR4,P-NF-κB p65,p-IκB-αprotein expression levels were unusually higher than the Control group(P<0.05).The pathological damage occurred in the kidney tissue,and the weight of fetal rats and weight of placenta were also unusually higher than the Control group(P<0.05).PPPs was able to unusually reduce FBG,blood lipids and renal function indexes,renal tissue inflammatory factor levels and renal tissue TLR4,p-NF-κB p65,p-IκB-αprotein expression levels in GDM rats(P<0.05),decrease the weight of fetal rats and weight of placenta(P<0.05),and reduce the pathological damage of kidney tissue.In addition,the effect of LPS on GDM rats was opposite to that of PPPs,and the effect of PPPs on GDM rats could be reversed by LPS.Conclusion PPPs can ameliorate the disorders of glucose and lipid metabolism and inflammation in GDM rats by inhibiting the TLR4/NF-κB signaling pathway,and protect the kidney from damage.