The Effects And Mechanisms Of Jinlida Granules On Hypothalamus-pituitary-thyroid Axis In Diabetic Rats Induced By STZ

Objective: diabetes mellitus(DM)and thyroid disease are common endocrine diseases.They are connection with clinical symptoms of multiple organs.DM increased incidence of thyroid dysfunction,and thyroid dysfunction aggravates DM clinical presentations and complications.Jinlida,one of representative of the traditional Chinese medicine does effect on diabetes through multiple pathways such as increasing secretion of insulin,alleviating insulin assistance and protecting islet beta cells.In spite of many clinical and animal studies demonstrate that the thyroid hormone will change in the following of suffering DM.But for the hypothalamus-pituitary-thyroid(HPT)axis hormone and its receptor change is still lack of systematic study,especially for diabetes,the role of thyroid hormone in thyroid hormone receptor,iodine enzymes and inflammatory pathways in the target tissues do not yet understand.In this study,inducing diabetic rats model through the chain of urea,to observe the change of hypothalamus-pituitary-thyroid axis(HPT)axis of diabetic rats after the intervention of the oral glucose-lowering drugs such as Jinlida,Metformin.And to study the mechanism of diabetes inducing thyroid dysfunction and Jinlida improving the HPT axis preliminary.Methods: 48 SD rats were randomly divided into diabetic group and normal group,The diabetic rats model is made by intraperitoneal injection streptozotocin(STZ,65mg/kg)one-time.Then the diabetic group was divided into blank control group(i.e.,no drug intervention group)and low-dose Jinlida in the intervention group,middle-dose Jinlida in the intervention group JH group,Met group,Sax group and Jinlida with tongxinluo prescription group.After the success of the modeling(6/group),to give the drug or placebo respectively in daily morning 8:00,8 weeks.rats after putting to death,blood samples,thyroid,Hypothalamus,pituitary and liver and other organ or tissue were collected.Adopting lectrochemical luminescence and ria method to detect serum fasting plasma glucose(FBG),the concentration of T3,T4 and TSH,Rt-PCR to detect expression of liver TH-r liver iodine enzyme(Dio1),sodium iodic transporter(NIS),TSH-r of thyroid,hypothalamic proTRH mRNArespectively.And western blot to detect the p I?B?pNF-?B?TNF? and IL-6 of liver tissue and HE staining of thyroid tissue.Results: 1.The weight of diabetic group was significantly lower than normal group(p<0,05),the diabetic group weight was similar with drugs intervention group.Blood glucose: FBG in diabetic group was higher than normal group(p<0.05),when comparing with diabetic group,JH group,Sax group and Jinlida + tongluo prescription group,Met group were desreased(p<0.05),the remaining groups were similar with diabetic group.2.The concentration of T3 and T4 was decreased significantly when compared with normal group(p<0.01),but expression of TSH and proTRH mRNA was no significant difference.As to drug intervention group,the concentration of T3 and T4 in JH group,JM+T group,Met group,Sax group were increased(p<0.05).the concentration of T4 in Met group was significantly increased(p<0.01).3.Expression of TH-R mRNA in rats liver was decreased(p<0.01)and expression of TSH-R mRNA was increased(p<0.01)when comparing with normal group.As to diabetic groups,TH-R mRNA in JH group,JM+T group was increase(p<0.01).Met group,Sax group were increased(p<0.05).TSH-R mRNA expression in middle-dose Jinlida group JH group,middle-dose Jinlida + tongxinluo group,Met group were increased compared with diabetic group(p<0.01).TSH-R mRNA expression in JL group,Sax group was increased compared with diabetic group(p<0.05).4.NIS mRNA expression in DM group was decreased compared with normal group(p<0.01).Compared with DM group,NIS mRNA expression in JM+T group and Met group were significantly increased(p < 0.01).NIS mRNA expression in JH group and Sax group were also increased(p < 0.05);These was no difference among JL group,JM group and DM group.5.Compared with normal group,DM group,the iodine enzyme Dio1 mRNA expression in rat liver was significantly lowered(p < 0.01);Compared with DM group,the iodine enzyme Dio1 mRNA expression in JH group,JM+Tgroup and Sax group was significantly lowered(p < 0.01),Dio1 mRNA expression in Met group is also lowered(p < 0.05);And JL group,JM group and DM group were no statistical difference.6.Compared with normal group,p I?B,TNF?(p<0.05),pNF-?B,and IL-6(p<0.01)levels in rat liver tissue of DM group were elevated.Compared with DM group,pI?B level in Met group and JM+T group were decreased(p < 0.05),the rest groups and DM group were no statistical difference.Compared with DM group,pNF-kB level in JH group,JM+T group and Met group were lower(p < 0.05),the remaining groups were no statistical difference.Compared with DM group,TNF? and IL-6 level in liver tissue in JM group,JM+T group and Met group were decreased(p < 0.05),the rest groups and DM group were also no statistical difference.7.DM group,average thyroid follicular epithelial height decrease,colloid area increase,follicular size decreases,and suggests that under diabetes,the thyroid hormone synthesis,absorb,secretion was damaged.JH group,JM+T group improved obviously.Conclusion: STZ induced diabetic rats showed NTIS presentations,T3,T4 decreased and TSH did not change significantly,Jinlida particles can improve the performance of HPT axis and the specific mechanism may improve the environment of inflammation of the liver,the NF kappa B pathway on the removal of inhibition of deiodinase(D1)and TR beta on reduction.