Study on the Effect and Mechanism of Bushen Huoxue Prescription on Rats with Endometrial Hyperplasia of Kidney Deficiency and Blood Stasis Type
10.19378/j.issn.1003-9783.2024.05.003
- VernacularTitle:补肾活血方对肾虚血瘀型子宫内膜增生症大鼠的作用及机制研究
- Author:
Haoyue LI
1
;
Xi WANG
;
Lei HAO
Author Information
1. 河北中医药大学药学院,河北 石家庄 050200
- Keywords:
Bushen Huoxue Prescription;
endometrial hyperplasia;
kidney deficiency and blood stasis syndrome;
MMP-9/TIMP-1 balance;
Bax;
Bcl-2;
PTEN;
rats
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2024;35(5):623-632
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect and mechanism of Bushen Huoxue Prescription(Morindae Officinalis Radix,Cuscutae Semen,Astragali Complanati Semen,Codonopsis Radix,Poria,etc.)on endometrial hyperplasia(EH)rats of kidney deficiency and blood stasis type.Methods A total of 90 SD rats were randomly divided into normal group,model group,Mifepristone group(12 mg·kg-1),and low-,medium-,and high-dose Bushen Huoxue Prescription groups(1.2,2.4,4.8 g·kg-1),with 15 rats in each group.The EH rat model of kidney deficiency and blood stasis type was replicated by intragastric administration of Hydroxyurea and Estradiol Valerate combined with tail vein injection of high molecular dextran.After successful modeling,each group was given intragastric administration according to the set dose,once a day for 21 consecutive days.At the end of the experiment,the levels of serum cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),cortisol(CORT),adrenocorticotropic hormone(ACTH),triiodothyronine(T3),thyroxine(T4),thyroid stimulating hormone(TSH),whole blood viscosity,hemorheology and coagulation function were detected by biochemical method.The levels of serum estrogen(E2),follicular estrogen(FSH),luteinizing hormone(LH),nitric oxide(NO)and endothelin-1(ET-1)were detected by ELISA.The pathological changes of endometrial tissue were observed by HE staining,and the endometrial thickness was measured.The protein expression levels of matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in endometrial tissues were detected by immunohistochemistry.The protein expression levels of MMP-9,TIMP-1,B-cell lymphoma 2(Bcl-2),Bcl-2 related X protein(Bax)and phosphatase and tensin homologue deleted on chromosome 10(PTEN)in endometrial tissue were detected by Western Blot.Results Compared with the normal group,the levels of serum CORT,ACTH,cAMP,T3,T4,TSH,ET-1 and ET-1/NO ratio in the model group were significantly decreased(P＜0.05,P＜0.01),while the levels of cGMP,E2,FSH,LH and NO were significantly increased(P＜0.05,P＜0.01).The indexes of hemorheology and fibrinogen(FIB)content were significantly increased(P＜0.05),and thrombin time(TT),prothrombin time(PT)and activated partial thromboplastin time(APTT)were significantly prolonged(P＜0.05).The uterine index and endometrial thickness were significantly increased(P＜0.01).The protein expressions of MMP-9 and Bcl-2 in endometrial tissue were significantly up-regulated(P＜0.01),and the protein expressions of TIMP-1,PTEN and Bax were significantly down-regulated(P＜0.01).Compared with the model group,the levels of serum CORT,ACTH,cAMP,T3,T4,TSH,ET-1 and ET-1/NO ratio in the Bushen Huoxue Prescription group were significantly increased(P＜0.05,P＜0.01).The levels of cGMP,E2,FSH,LH and NO were significantly decreased(P＜0.05,P＜0.01).The indexes of hemorheology and FIB content were significantly decreased(P＜0.05,P＜0.01),and TT,PT and APTT were significantly shortened(P＜0.05).The uterine index and endometrial thickness were significantly decreased(P＜0.05,P＜0.01).The protein expressions of MMP-9 and Bcl-2 in endometrial tissue were significantly down-regulated(P＜0.05,P＜0.01),and the protein expressions of TIMP-1,PTEN and Bax were significantly up-regulated(P＜0.05,P＜0.01).Conclusion Bushen Huoxue Prescription can improve the symptoms and signs of EH rats with kidney deficiency and blood stasis,protect endometrial vascular endothelial function,and alleviate endometrial hyperplasia.Its mechanism is related to the restoration of MMP-9/TIMP-1 balance,up-regulation of Bax and PTEN expressions,and inhibition of Bcl-2 expression.
