| Background:Polycystic ovary syndrome(PCOS)is a multi-system disease involving reproductive,endocrine and metabolic abnormalities.Existing studies believe that the pathogenesis of PCOS is related to epigenetic,inflammatory,oxidative stress and other pathological mechanisms,but its pathogenesis is not completely clear at present.In addition,the clinical manifestations of PCOS are highly heterogeneous,and the existing therapeutic drugs mainly focus on symptomatic treatment,which cannot meet its clinical needs.Therefore,it is necessary to understand the research trends and hot spots of PCOS for the subsequent research.PCOS combined with IR is an important clinical phenotype.IR can aggravate ovulation disorder,HA,lipid metabolism disorder and other pathological links of PCOS,playing a role in the pathogenesis of PCOS.Studies have shown that the occurrence of PCOS IR is related to the dysfunction of PI3K/AKT/GLUT4 and other classical insulin signaling pathways.Banxia Xiexin Decoction,from the Treatise on Miscellaneous Diseases of Typhoid Fever,is a classic acrid opening and bitter downbearing prescription of Zhongjiao.Its pathogenesis is stomach heat and spleen deficiency.Our research group’s previous study found that PCOS IR patients are mostly stomach heat and spleen deficiency.The application of Jiaying Banxia Xiexin Decoction in the treatment of PCOS IR patients with stomach heat and spleen deficiency can intervene in ovulation,androgen increase,IR and other aspects,but there is still room for further improvement of clinical efficacy.And our research group has confirmed through animal experiments that the addition or reduction of Banxia Xiexin decoction improves IR by regulating PI3K/AKT/GLUT4 signaling pathway.Through literature review,this study combined the use of electroacupuncture(Guanyuan and Sanyinjiao)on the basis of addition and reduction of Banxia Xiexin Decoction in order to further improve the clinical efficacy,and continue to explore the mechanism of its improvement of ovulation disorder in PCOS IR patients on the basis of previous animal experimental studies.Objective:1.Bibliometric analysisBy means of bibliometrics,the cooperative relationship between authors,institutions and countries in the field of PCOS research in the past 30 years is presented,and the visualization analysis of keywords is carried out to explore the hot spots in the field of PCOS research,so as to provide references for the clinical and basic research of PCOS.2.Clinical researchIt aimed to objective evaluated the efficacy and safety of combination of acupuncture and traditional Chinese medicine(TCM)for PCOS IR with stomach heat and spleen deficiency type,and more effective treatment methods were explored to meet the clinical needs of PCOS,providing reference for the follow-up studies of PCOS.3.Experimental researchExperimental research aims to explore the mechanism of electroacupuncture(Guanyuan and Sanyinjiao)combined with Banxia Xiexin Decoction in the treatment of IR ovulation disorder of PCOS from the perspective of follicular angiogenesis with HIF-1/VEGF/Notch signaling pathway as the entry point,and provide new targets and ideas for the prevention and treatment of PCOS by traditional Chinese medicine.Methods:1.Bibliometric analysisThe literature on PCOS from January 1990 to July 2022 was retrieved through the Web of Science Core Collection(WoSCC)database and imported into CiteSpace in plain text format.Visualization analysis of authors,countries,institutions,highly cited literature and keywords was carried out to reveal the hot spots and trends in the field of PCOS.2.Clinical researchA total of 56 patients with PCOS who met the inclusion criteria and did not meet the exclusion criteria were selected from the Department of Gynecology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences from December 2020 to June 2022.They were randomly divided into acupuncture combined with TCM group and TCM group by random envelope method.The acupuncture combined with TCM group were treated with electroacupuncture(Guanyuan and Sanyinjiao)combined with Banxia Xiexin Decoction.The TCM group was treated with Banxia Xiexin Decoction alone,and the treatment cycle was 3 months.Venous blood was drawn before and after treatment.The main efficacy indexes(cumulative BBT biphasic rate,BBT periodic biphase ratio,FINS,P1h-INS,P2h-INS,area under the insulin curve),and secondary efficacy indexes(female reproductive hormone.menstrual cycle rate,menstrual cycle score,TCM symptom score,glycemic metabolism related indexes,BMI,waist circumference,hip circumference,WHR.four items of blood lipids,PCOSQ,SCL-90,SAS,SDS)were compared between the two groups before and after treatment.3.Experimental researchA total of thirty-six 6-week-old female SPF SD rats were randomly divided into two groups:blank group(group E)with 9 rats and model group with 27 rats.The PCOS IR rat model was constructed by letrozole combined with high fat diet.After the modeling,3 rats were taken from each blank group(group E0)and model group(group M0)to verify the modeling results.After successful modeling,24 model group rats were randomly divided into 4 groups:model group(group M),clomiphene group(group X),acupuncture combined with TCM group(group C),and TCM group(group T),and intervention for 2 weeks.After treatment.sex hormones and insulin were detected by ELISA,blood lipids were detected by biochemical method,ovarian histopathology was observed by HE staining,follicular capillaries were labeled with CD34 antibody for follicular capillaries count,and expressions of HIF-1/VEGF/Notch signaling pathway related factor genes and proteins were detected by RT-PCR and immunohistochemistry.Results:1.Bibliometric analysisFrom 1990 to 2022,a total of 18,377 articles were retrieved in the field of PCOS.The United States made the largest contribution to the field of PCOS,with Legro RS as the leading author and Monash University as the leading institution.The PCOS Consensus Seminar group sponsored by ESHRE/ASRM Rotterdam was published in Fertil Steril journal in 2004 and has the most cited literature.Key words analysis showed that hyperandrogenemia plays a central role in the pathological link of PCOS,and endothelial function,granulosa cells,follicular fluid and oxidative stress may be the focus of future research on the pathological mechanism of PCOS.2.Clinical research(1)BBT biphase ratio:The cumulative biphasic rate of BBT was 78.57%in the acupuncture combined with TCM group and 67.86%in the TCM group,there was no significant difference between the two groups(P>0.05).The biphasic rate of BBT cycle was 50.00%in the acupuncture combined with TCM group and 34.50%in the TCM group,which was significantly higher between two groups(P<0.05).(2)Serum insulin level:Compared with before treatment,FINS,P2h-INS and HOMA-IR were significantly decreased(P<0.05)in acupuncture combined with TCM group,FINS were significantly decreased(P<0.05)in TCM group.There was no significant difference between the two groups after treatment(P>0.05).(3)Female reproductive hormone:Compared with before treatment,T and AN in the acupuncture combined with TCM group and the TCM group were significantly decreased(P<0.05),LH/FSH in the TCM group was significantly decreased(P<0.05).There were no significant differences in FSH,LH,E2.PRL,DHEA-S indexes between the two groups after treatment(P>0.05).(4)The rate of menstrual cycle:The rate of menstrual cycle was 71.43%in the acupuncture combined with TCM group and was 66.67%in the TCM group,and compared with the TCM group,there was no significant difference between the two groups(P>0.05).(5)Menstrual cycle scores:Compared with before treatment,menstrual cycle scores in both groups decreased significantly after treatment(P<0.001).There was no significant difference in menstrual cycle scores between the two groups after treatment(P>0.05).(6)TCM symptom score:Compared with before treatment,the in TCM symptom score in both groups decreased significantly after treatment(P<0.01).There was no significant difference in TCM symptom score between the two groups after treatment(P>0.05).(7)OGTT:Compared with before treatment,there were no significant differences in the area under the glucose curve,FPG,P1h-FPG,P2h-FPG between the two groups after treatment(P>0.05).There was no significant difference between the two groups after treatment(P>0.05).(8)Physical index:Compared with before treatment,body weight,BMI and waist circumference were significantly decreased(P<0.05)in the acupuncture combined with TCM group;Body weight and BMI were significantly decreased(P<0.05)in TCM group;There was no significant change in WHR between the two groups(P>0.05).There was no significant difference in the indexes between the two groups after treatment(P>0.05).(9)Lipid metabolism index:Compared with before treatment,CHO,TG,LDL-C and HDL-C in both groups had a decreasing trend(P>0.05).There was no significant difference between the two groups after treatment(P>0.05).(10)Score of PCOSQ,SCL-90,SAS and SDS:Compared with before treatment,PCOSQ score was significantly increased(P<0.05),SCL-90 and SAS scores were significantly decreased(P<0.05)and SDS score had a decreasing trend(P>0.05)in acupuncture combined with TCM group,PCOSQ score was significantly increased(P<0.05)and SCL-90,SAS and SDS scores had a downward trend(P>0.05)in TCM group.After treatment,there was no significant difference between the two groups(P>0.05).(11)Security Index:Compared with before treatment,there were no significant differences in ALT,AST,Cr and UREA between the two groups after treatment(P>0.05).There was no significant difference between the two groups after treatment(P>0.05).3.Experimental research(1)Modeling results:Compared with E0 group,body weight,T,LH/FSH and HOMA-IR in M0 group increased significantly,and HE staining showed a large number of cystic dilated follicles with significantly reduced granulosa cell layer,indicating successful construction of PCOS IR model.(2)Body weight:Compared with group E,body weight of group M increased significantly on day 0,day 7 and day 14 after treatment(P<0.01).Compared with group M,body weight in group C decreased significantly at 14 days after treatment(P<0.05).(3)Reproductive hormones:Compared with group E,LH,T and LH/FSH in group M were significantly increased(P<0.05),while E2 had a downward trend(P>0.05).Compared with group M,LH/FSH in group X was significantly decreased(p<0.05);In T group,LH,T and LH/FSH were significantly decreased(P<0.05);T and LH/FSH in group C were significantly decreased(P<0.05).(4)Glucose metabolism indexes:Compared with group E,FINS and HOMA-IR in group M were significantly increased(P<0.01).Compared with group M,FINS and HOMA-IR in groups T and C were significantly decreased(P<0.01).(5)Lipid metabolism indexes:compared with group E,TG and LDL-C in group M were significantly increased(P<0.05),CHO had an increasing trend(P>0.05).Compared with group M,CHO and LDL-C in group X were significantly decreased(P<0.05).CHO and TG in T group were significantly decreased(P<0.05).TG in group C was significantly decreased(P<0.05).(6)Ovarian histopathology:follicles and corpus luteum at different stages of development were observed in group E,and granulosa cells presented multiple layers,without cystic dilated follicles.In group M,the follicle structure was abnormal,no mature follicles were observed,a large number of cystic dilated follicles were observed and the granulosa cell layer was reduced.The follicle morphology of X,T and C groups was improved,and the number of granular cell layers was increased.(7)follicles microvascular count:Immunohistochemical results showed that compared with group E,M group of early tertiary follicle significantly reduce the number of capillaries(P<0.05).Compared with group M,the number of capillaries in group X and group C was significantly increased(P<0.05),and the number of capillaries in group T had an upward trend(P>0.05).(8)HIF-1/VEGF/Notch signaling pathway gene expression:RT-PCR showed that compared with group E,HIF-1α and VEGF mRNA levels in group M were significantly decreased(P<0.05),and Notch-2,Jagged 1,DLL4 and VEGFR2 mRNA levels were decreased(P>0.05).Compared with group M,HIF-1α,VEGF,Notch2,Jagged 1 and DLL4 mRNA levels of in group X were significantly increased(P<0.05),the all indexes mRNA levels in groups T and C had an increasing trend(P>0.05),VEGFR2 mRNA levels in T group was significantly increased(P<0.05).HIF-1α and VEGFR2 mRNA levels in group C were significantly increased(P<0.05).(9)HIF-1/VEGF/Notch signal pathway of protein expression:immunohistochemical detection results showed that compared with group E,the protein levels of HIF-1α,VEGF,Notch2,Jaggedl,DLL4 and VEGFR2 in group M were significantly decreased(P<0.05).Compared with M group,the protein levels of HIF-1α,Notch2,DLL4 and VEGFR2 in groups X,T and C were significantly increased(P<0.05).The VEGF protein level in groups X and C was significantly increased(P<0.05),and the VEGF protein level in group T had an increasing trend(P>0.05).The Jaggedl protein level in X group and C group was significantly increased,and the Jagged1 protein level in T group had an increasing trend(P>0.05).Conclusion1.The number of papers published in the field of PCOS research showed an increasing trend.It is necessary to strengthen cooperation among various authors,countries and institutions,increase the research on the mechanism of PCOS,and develop universally recognized diagnostic criteria and consensus for PCOS.Endothelial dysfunction,granulosa cells,follicular fluid and oxidative stress may be the future mechanisms of PCOS.2.Electroacupuncture(Guanyuan and Sanyinjiao)combined with Banxia Xiexin Decoction can restore spontaneous ovulation in PCOS IR patients,promote menstruation,improve IR,reduce androgen levels,improve clinical symptoms,improve quality of life,and improve anxiety state.It can take into account multiple pathological links of PCOS,and is superior to traditional Chinese medicine treatment alone in improving ovulation.In addition,the combination of needle and drug therapy for PCOS IR has certain safety.3.Electroacupuncture(Guanyuan and Sanyinjiao)combined with Banxia Xiexin Decoction can increase the number of follicular microvessels,improve the follicular blood transport and restore spontaneous ovulation of PCOS by regulating HIF-1/VEGF/Notch signaling pathway in PCOS IR rats. |
PDF Full Text Request