鹿茸对氢化可的松及腺嘌呤诱导肾阳虚证大鼠HPG/HPA轴的差异性调控研究OA

Objective This study aimed to investigate the differential regulatory effects of Cervi Cornu Pantotrichum(CCP)on the hypothalamic-pituitary-gonadal(HPG)and hypothalamic-pituitary-adrenal(HPA)axes using two distinct rat models of kidney-yang deficiency induced by hydrocortisone and adenine.Methods The protein composition of CCP was analyzed using liquid chromatography-mass spectrometry.Male SD rats were modeled with hydrocortisone and adenine,and monitored for physical signs,dietary changes,mating and endurance behavior,and sperm quality after 6 weeks of CCP administration.Rat serum was assayed for cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),testosterone(T),estradiol(E2),adrenocorticotropic hormone(ACTH),corticosterone(CORT),catalase(CAT),malondialdehyde(MDA),interleukin(IL)-6,tumor necrosis factor(TNF)-α,and other indicators.Reverse transcription-quantitative PCR was used to detect the expression levels of ADCY2,PKA,AC1,EDNRB,CCKBR,and other genes in brain tissue.Results CCP protein was primarily composed of collagen.Compared with the Control Ⅰ group,the Model Ⅰ group exhibited a significantly decreased serum cAMP level and a significantly increased cGMP level(P＜0.05).Mating frequency and sperm motility were significantly reduced(P＜0.05),and the T level was significantly decreased(P＜0.05).Hanging time was significantly reduced(P＜0.01),and ACTH and CORT levels were significantly decreased(P＜0.05 and P＜0.01).Creatine(CREA)and urea nitrogen(UREA)levels were significantly increased(P＜0.05 and P＜0.01).CAT activity was significantly decreased(P＜0.01),whereas MDA,IL-6,and TNF-α levels were significantly elevated(P＜0.001).Following treatment with CCP,these indicators all improved to varying degrees.The regulatory effect of the adenine-induced model on the HPG axis was significantly stronger than that of the hydrocortisone-induced model.Compared with the Control Ⅱ group,the Model Ⅱ group showed significantly decreased cAMP levels(P＜0.001)and significantly increased cGMP levels(P＜0.01).Sperm viability and T and E2 levels were significantly decreased(P＜0.01),as were ACTH and CORT levels(P＜0.05 and P＜0.01).CREA,UREA,uric acid(UA),and cystatin C(Cys C)levels were all significantly increased(P＜0.01,P＜0.001).CAT activity was significantly reduced(P＜0.001),whereas MDA,IL-6,and TNF-α levels were significantly elevated(P＜0.01,P＜0.001).After CCP treatment,these indicators all improved to varying degrees.In the hydrocortisone-induced model,comprehensive downregulation of genes within the cerebral cAMP pathway was observed,including ADCY2.In contrast,the adenine-induced model showed suppressed expression of ADCY2,PKA,and AC1 alongside upregulated expression of EDNRB and CCKBR.Following CCP intervention,cAMP pathway expression was reversed in both models.Additionally,the upregulated expression of EDNRB and CCKBR in the adenine-induced model was inhibited by CCP treatment,suggesting that CCP ameliorates neuro-molecular abnormalities induced by different etiologies through a multitarget mechanism.Conclusions Hydrocortisone-induced Kidney-yang deficiency primarily involves HPA-axis suppression,whereas adenine-induced Kidney-yang deficiency mainly affects the HPG axis and causes target organ damage.CCP restored HPG/HPA axis function by repairing structures and promoting hormone secretion,regulating cAMP pathways,correcting abnormal EDNRB and CCKBR expression in adenine-induced rats,and improving renal fibrosis and inflammation.These findings suggest that CCP has comprehensive therapeutic effects,particularly in models involving multisystem damage.