Effects of Jianpi Huatan Prescription on Cholesterol Synthesis in Liver of Subclinical Hypothyroidism Mice Based on cAMP/CREB/HMGCR Signaling Pathway
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 deposition,and its mechanism may be to reduce TSH levels in SCH mice by regulating the cAMP/CREB/HMGCR signaling pathway.
万方数据
维普
