天麻素通过激活GPR120/AMPK通路改善妊娠期糖尿病大鼠母胎界面损伤OA
Gastrodin Ameliorates Maternal-fetal Interface Injury in Gestational Diabetes Mellitus Rats by Activating the GPR120/AMPK Pathway
目的 探究天麻素对妊娠期糖尿病(GDM)大鼠母胎界面脂毒性损伤的作用及机制.方法 采用腹腔注射链脲佐菌素法构建GDM大鼠模型,30 只妊娠大鼠随机分为模型组、天麻素组(100 mg/kg)和天麻素(100 mg/kg)+G蛋白偶联受体 120(GPR120)拮抗剂AH7614(25 mg/kg)组,每组 10 只.另取 10 只妊娠大鼠作为对照组.各组通过腹腔注射或灌胃相应药物,每天 1 次连续至妊娠第 20 天.检测血清空腹血糖(FBG)、游离脂肪酸(FFA)、总胆固醇(TC)、甘油三酯(TG)水平及母体体质量、胎鼠存活率;ELISA、免疫组化法分别检测血清及母胎界面组织TNF-α、IL-1β水平;流式细胞术检测母胎界面组织中细胞凋亡水平;免疫双荧光法检测母胎界面组织GPR120、腺苷酸活化蛋白激酶(AMPK)蛋白分布及表达;Western blot检测母胎界面组织GPR120、AMPK、磷酸化AMPK(p-AMPK)蛋白表达.结果 与对照组比较,模型组大鼠血清FBG、FFA、TC、TG、TNF-α、IL-1β,母体体质量,母胎界面组织TNF-α、IL-1β、细胞凋亡水平均升高(P<0.05);胎鼠存活率,母胎界面组织GPR120、p-AMPK/AMPK水平均降低(P<0.05).与模型组比较,天麻素组大鼠血清FBG、FFA、TC、TG、TNF-α、IL-1β,母体体质量,母胎界面组织TNF-α、IL-1β、细胞凋亡水平均降低(P<0.05);胎鼠存活率,母胎界面组织GPR120、p-AMPK/AMPK水平均升高(P<0.05).AH7614 可逆转天麻素对GDM大鼠的干预效果(P<0.05).结论 天麻素可改善GDM大鼠糖脂代谢、肥胖及不良妊娠结局,抑制母胎界面炎症和细胞凋亡,其作用机制可能与激活GPR120/AMPK通路有关.
Objective To investigate the effects and mechanisms of gastrodin on lipotoxicity damage at the maternal-fetal interface in rats with gestational diabetes mellitus(GDM).Methods A GDM rat model was established using intraperitoneal injection of streptozotocin.Thirty pregnant rats were randomly divided into three groups:model group,gastrodin group(100 mg/kg),and gastrodin(100 mg/kg)+G protein-coupled receptor 120(GPR120)antagonist AH7614(25 mg/kg)group.An additional 10 pregnant rats were used as a control group.Each group received intraperitoneal injection or gavage of corresponding drugs once daily until the 20th day of pregnancy.Serum fasting blood glucose(FBG),free fatty acids(FFA),total cholesterol(TC),and triglycerides(TG)levels,as well as maternal body weight and fetal survival rate,were measured.ELISA and immunohistochemistry were used to measure serum and maternal-fetal interface tissue TNF-α and IL-1β levels.Flow cytometry was used to detect cell apoptosis in maternal-fetal interface tissue.Immunofluorescence was used to detect GPR120 and adenosine monophosphate-activated protein kinase(AMPK)protein distribution and expression.Western blot was used to detect GPR120,AMPK,and phosphorylated AMPK(p-AMPK)protein expression in maternal-fetal interface tissue.Results Compared with the control group,the model group showed significantly increased serum FBG,FFA,TC,TG,TNF-α,and IL-1β,maternal body weight,maternal-fetal interface tissue TNF-α,IL-1β,and cell apoptosis levels(P<0.05),while fetal rat survival rate and maternal-fetal interface tissue GPR120 and p-AMPK/AMPK levels were significantly decreased(P<0.05).Compared with the model group,the gastrodin group showed significantly decreased serum FBG,FFA,TC,TG,TNF-α,and IL-1β,maternal body weight,maternal-fetal interface tissue TNF-α,IL-1β,and cell apoptosis levels(P<0.05),while fetal rat survival rate and maternal-fetal interface tissue GPR120 and p-AMPK/AMPK levels were significantly increased(P<0.05).AH7614 reversed the intervention effect of gastrodin on GDM rats(P<0.05).Conclusion Gastrodin can improve glucose and lipid metabolism,obesity,and adverse pregnancy outcomes in GDM rats,inhibit inflammation and apoptosis at the maternal-fetal interface,and its mechanism may be related to the activation of the GPR120/AMPK pathway.
李楠;牛子怡;邵岚
石家庄市妇幼保健院产科,河北 石家庄 050000石家庄市妇幼保健院产科,河北 石家庄 050000石家庄市妇幼保健院产科,河北 石家庄 050000
医药卫生
天麻素妊娠期糖尿病母胎界面糖脂代谢脂毒性GPR120/AMPK信号通路大鼠
GastrodinGestational diabetes mellitusMaternal-fetal interfaceGlucose and lipid metabolismLipotoxicityGPR120/AMPK signaling pathwayRats
《昆明医科大学学报》 2026 (2)
43-50,8
河北省卫生健康委员会科研项目(20231345)
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