基于cAMP/CREB/HMGCR信号通路研究健脾化痰方对亚临床甲状腺功能减退症小鼠肝脏胆固醇合成的影响  

Effects of Jianpi Huatan Prescription on Cholesterol Synthesis in Liver of Subclinical Hypothyroidism Mice Based on cAMP/CREB/HMGCR Signaling Pathway

作　　者：罗鹏 徐航 阮琳[2] 闵冬雨[3] 高天舒[3] 贾连群[1] 武跃华[2] 陈巍[1,2] LUO Peng;XU Hang;RUAN Lin;MIN Dongyu;GAO Tianshu;JIA Lianqun;WU Yuehua;CHEN Wei(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属第二医院,辽宁沈阳110034 [3]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《中国中医药信息杂志》2025年第1期85-90,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金(82004340);辽宁省教育厅高等学校基本科研项目(2100221283);辽宁省博士启动金计划项目(2020-BS-045);辽宁省“兴辽英才计划”项目(XLYC2007076)。

摘　　要：目的观察健脾化痰方对亚临床甲状腺功能减退症(SCH)小鼠肝脏胆固醇合成的影响,基于cAMP/CREB/HMGCR信号通路探讨其作用机制。方法将80只雄性C57BL/6小鼠随机分为对照组10只和造模组70只,造模组予甲巯咪唑0.08mg/(kg·d)饮水喂养16周建立SCH模型。将成模小鼠随机分为模型组、优甲乐组和健脾化痰方高、中、低剂量组,每组10只,分别予相应药物灌胃6周。HE染色、油红O染色分别观察小鼠肝组织形态和脂质沉积情况,ELISA检测血清促甲状腺激素(TSH)、三碘甲状腺原氨酸(T3)、甲状腺激素(T4)、总胆固醇(TC)、三酰甘油(TG)含量和肝组织TC、环磷酸腺苷(cAMP)含量,Western blot检测肝组织蛋白激酶A(PKA)、环磷腺苷反应元件结合蛋白(CREB)、p-CREB、3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)蛋白表达。结果与对照组比较,模型组小鼠肝组织出现大小不一脂肪空泡,脂质沉积明显;血清TSH、TC、TG及肝组织TC、cAMP含量明显升高(P<0.05,P<0.01);肝组织PKA、p-CREB、HMGCR蛋白表达明显升高(P<0.01)。与模型组比较,优甲乐组和健脾化痰方高、中剂量组小鼠肝组织脂质沉积情况和肝细胞结构不同程度改善,血清TSH、TC、TG及肝组织TC、cAMP含量降低(P<0.05,P<0.01);肝组织PKA、p-CREB、HMGCR蛋白表达明显升高(P<0.01)。结论健脾化痰方能明显抑制SCH小鼠肝脏胆固醇合成,改善肝脏脂肪空泡和脂质沉积,其机制可能是通过调控cAMP/CREB/HMGCR信号通路降低SCH小鼠TSH水平。Objective To observe the effects of Jianpi Huatan Prescription on hepatic cholesterol synthesis in subclinical hypothyroidism(SCH)mice;To discuss its mechanism based on cAMP/CREB/HMGCR signaling pathway.Methods Totally 80 C57BL/6 male mice were randomly divided into control group(10 mice)and modeling group(70 mice),and the modeling group was given methimazole 0.08 mg/(kg·d)in drinking water for 16 weeks to establish a SCH mdoel.The model mice were randomly divided into model group,euthyrox group and Jianpi Huatan Prescription high,medium-and low-dosage groups,with 10 mice in each group,and were given corresponding drugs for gavage for 6 weeks.HE staining and Oil red O staining were used to observe the morphology and lipid deposition of liver tissue,ELISA was used to detect serum contents of thyroid stimulating hormone(TSH),triiodothyronine(T3),thyroid hormone(T4),total cholesterol(TC),triglycerides(TG),and TC,cyclic adenosine monophosphate(cAMP)in liver tissue,Western blot was used to detect the expressions of protein kinase A(PKA),cyclic adenosine response element binding protein(CREB),p-CREB and 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)in liver tissue.Results Compared with the control group,the liver tissue of mice in the model group showed fat vacuoles of different sizes and obvious lipid deposition;the contents of TSH,TC,TG in serum and TC,cAMP in liver tissue significantly increased(P<0.05,P<0.01);the protein expressions of PKA,p-CREB and HMGCR significantly increased(P<0.01).Compared with the model group,lipid deposition in liver tissue and structure of liver cells was improved to varying degrees in euthyrox group and Jianpi Huatan Prescription high-and medium-dosage groups,and the contents of serum TSH,TC,TG,and liver tissue TC,cAMP decreased(P<0.05,P<0.01);the expressions of PKA,p-CREB and HMGCR protein in liver tissue increased significantly(P<0.01).Conclusion Jianpi Huatan Prescription can significantly inhibit hepatic cholesterol synthesis in SCH mice,and improve hepatic fat vacuoles and lipid d

关 键 词：亚临床甲状腺功能减退症 健脾化痰方 胆固醇合成 cAMP/CREB/HMGCR信号通路 小鼠 

分 类 号：R285.5[医药卫生—中药学]