目的 探讨山柰酚(kaempferol,Kpf)调节白细胞介素-6(interleukin-6,IL-6)/信号转导与转录激活子 3(signal transducer and activator of transcription 3,STAT3)信号通路对妊娠糖尿病(gestational dia-betes mellitus,GDM)大鼠炎症反应的影响.方法 雌雄同笼与高脂高糖喂养联合腹腔注射链脲佐菌素(streptozotocin,STZ)构建GDM大鼠模型,将造模成功大鼠按照随机数字表达分为Model组、Kpf低、中、高剂量组、激活剂组(IL-6/STAT3通路激活剂rIL-6),每组12只,同批12只妊娠大鼠作为control组,各组腹腔注射相应药物,每天1次,直到妊娠19 d.罗氏血糖仪测量大鼠空腹血糖(fasting blood glucose,FBG);分析各组大鼠妊娠结局;ELISA法测定大鼠血清空腹胰岛素(fasting insulin,FINS)及胎盘中白细胞介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)水平;苏木精伊红(hematoxylin-eosin,HE)染色观察大鼠胎盘组织中病理损伤;TUNEL染色检测胎盘组织细胞凋亡;蛋白质印迹测定胎盘中IL-6/STAT3通路蛋白表达.结果 与control组比较,Model组大鼠FBG、FINS、HOMA-IR、胎鼠质量、IL-6、IL-1β、TNF-α水平、胎盘组织IL-6、p-STAT3/STAT3水平及细胞凋亡率增加,活胎率、窝产子数下降(P＜0.05);相较于Model组,Kpf低、中、高剂量组大鼠FBG、FINS、HOMA-IR、胎鼠质量、IL-6、IL-1β、TNF-α水平、胎盘组织IL-6、p-STAT3/STAT3水平及细胞凋亡率下降,活胎率、窝产子数增加(P＜0.05);相较于Kpf高剂量组,激活剂组上述指标变化均显著逆转(P＜0.05).结论 Kpf可能通过抑制IL-6/STAT3信号通路降低GDM大鼠胎盘炎症,减轻胰岛素抵抗.
Effect of Kaempferol on Inflammatory Response in Rats with Gestational Diabetes Mellitus via Regulation of IL-6/STAT3 Signaling Pathway
Objective To investigate the effect of kaempferol(Kpf)on inflammatory response in rats with gestational diabetes mellitus(GDM)by regulation of the interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A rat model of GDM was constructed by the combination of high fat and high sugar diets and intraperitoneal injec-tion of streptozotocin(STZ).GDM rats were then randomly divided into 5 groups:Model group,Kpf low-,medium-,and high-dose groups,and activator group(IL-6/STAT3 pathway activator rIL-6),with 12 rats in each group,another 12 rats without any special treatment as the con-trol.Intraperitoneal injection of the corresponding drug was performed once a day until the 19th day of pregnancy.Roche blood glucose meter was applied to measure fasting blood glucose(FBG)in rats.The pregnancy outcomes of rats in each group were analyzed.ELISA method was applied to de-termine the levels of fasting insulin(FINS)in rat serum and interleukin-6,interleukin-1 β(IL-6,IL-1β),and tumor necrosis factor-α(TNF-α)in placental tissues.Hematoxylin-eosin(HE)staining was applied to observe pathological damage in rat placental tissues.TUNEL staining was ap-plied to detect apoptosis in placental tissues.The expression levels of IL-6/STAT3 pathway proteins in placental tissues were detected by Western blotting.Results The values of FBG,FINS,HO-MA-IR,fetal mouse weight,the levels of IL-6,IL-1β,TNF-α,the apoptosis rate of placental tissue cells,the expression levels of IL-6,p-STAT3/STAT3 proteins in the Model group were in-creased when compared with those in the control group,while the live birth rate and the number of offspring were decreased when compared with those in the control group(P＜0.05).The values of FBG,FINS,HOMA-IR,fetal mouse mass,the levels of IL-6,IL-1 β,TNF-α,the apoptosis rate of placental tissue cells,and the expression levels of IL-6,p-STAT3/STAT3 proteins in the Kpf low-,medium-,and high-dose groups were decreased when compared with those in the Model group,while the live birth rate and the number of offspring were increased when compared with those in the Model group(P＜0.05).The changes of the above indicators in the activator group were reversed when compared to the Kpf high-dose group(P＜0.05).Conclusion Kpf can allevi-ate placental inflammation and insulin resistance in GDM rats.Its mechanism may be related to the inhibition of IL-6/STAT3 signaling pathway.
gestational diabetes mellituskaempferolinterleukin-6signal transduction and activator of transcription 3inflammationinsulin resistance
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