| Polycystic ovary syndrome(PCOS)is the most common and complex endocrine disease in gynecology.Abnormal follicular development is the main pathophysiological feature of PCOS.Autophagy of ovarian granulosa cells is related to abnormal follicular development,but the specific mechanism has not yet been determined.The clinical effect of acupuncture in the treatment of PCOS has been clear,but the research on the target and the effective way of acupuncture in the treatment of PCOS is still in the initial stage of exploration,and in-depth high-quality research is very limited.Therefore,research on the mechanism of acupuncture treatment of PCOS is the direction that our Chinese medical community should pay attention to in the future,and it is also the foundation of this paper.Part I: Literature Study on Polycystic Ovarian Syndrome ObjectiveTo discuss the research progress of polycystic ovary syndrome and acupuncture therapy from the perspective of literature,and establish the experimental contents.MethodsSearched the PCOS literature reported at home and abroad in recent years comprehensively,systematically collated and summarized,and then grasped the frontier trends of PCOS research and acupuncture therapy.Results(1)Understanding,diagnosis and treatment of polycystic ovary syndrome in western medicine: the trend of PCOS incidence is increasing year by year,seriously endangering human health and increasing medical burden.So far,the pathogenesis of PCOS in modern medicine has been mainly explained from the following aspects:(1)ovarian autocrine-paracrine system,(2)"HPA" axis(hypothalamus-pituitary-ovarian reproductive axis)or "HPO" system(hypothalamus-pituitary-adrenal reproductive axis),(3)the network system of ovarian local signal transduction pathways,(4)environmental and psychological factors,(5)five aspects of genetic factors.In the clinical treatment of PCOS in western medicine,symptomatic treatment is mostly aimed at a single clinical manifestation of PCOS.(2)The understanding,diagnosis,treatment,and research progress of polycystic ovary syndrome in Chinese medicine: PCOS is also called menstrual disease and infertility in Chinese medicine.which has been recorded for a long time in the history of Chinese culture.Therefore,Chinese medical doctors and later Chinese medical scholars Both have accumulated rich clinical experience in the treatment of PCOS,conducted experimental deepening research,and had made great contributions to the medical career.(3)Research on the mechanism of acupuncture in the treatment of polycystic ovary syndrome: A large number of literatures show that acupuncture has a clear clinical effect in the treatment of PCOS,and its mechanism of action is closely related to improve the pathogenesis of PCOS,including:(1)Improving the ovarian microenvironment and cytokine expression to promote Ovulation,(2)Improving the body’s metabolism-improve insulin resistance and hyperinsulinemia,reducing body mass and the level of leptin in the body,(4)regulating the function of the hypothalamus-pituitary-ovarian axis(HPO)or adrenal cortex axis(HPA),(5)Local stimulation of acupuncture can promote o v u l a t i o n,(6)i m p r o v i n g e n d o m e t r i a l r e c e p t i v i t y,h e l p i n g e m b r y o implantation,changing the outcome of pregnancy,(7)improving the mental and psychological state of patients.(4)Project basis and research content:(1)Abnormal follicular development is an important pathological manifestation of polycystic ovary syndrome,(2)Autophagy of ovarian granulosa cells is an important factor in abnormal follicular development,(3)Studies have confirmed that Lnc MEG3 participates in the regulation of tissues and cells autophagy,(4)PI3K/AKT/m TOR signaling pathway is a classic pathway which regulating autophagy,(5)Lnc MEG3 In summary,we proposed a hypothesis: Acupuncture could mediate the PI3K/AKT/m TOR pathway to regulate the occurrence of autophagy in ovarian granulosa cells by regulating the expression of Lnc MEG3,improving follicular development,and achieving the effect of treating PCOS ovulation disorders.ConclusionResearch on the pathogenesis of polycystic ovary syndrome and the mechanism of acupuncture treatment of PCOS is in the preliminary stage,and further exploration is needed.In order to further improve the mechanism of acupuncture in the treatment of polycystic ovary syndrome,this topic selects Lnc MEG3 and granulosa cell autophagy as the entry point,and observes the overall theory of acupuncture on PCOS from macro to micro by testing relevant indicators,and further proving its therapeutic effect and the mechanism of action.Part Two: Experimental Research ObjectiveTo clarify that acupuncture can treat PCOS ovulation disorders by improving follicle development;verify that Lnc MEG3 can regulate autophagy in ovarian granulosa cells through the PI3K/AKT/m TOR pathway;confirm that acupuncture can affect the expression of Lnc MEG3,and then regulate ovarian granules autophagy through the PI3K/AKT/m TOR pathway,affect the development of follicles to achieve the effect of curing PCOS ovulation disorders;reveal the mechanism of acupuncture on polycystic ovary syndrome.Methods(1)Using PCOS rats as the model,detected the serum T,FSH,AMH,LH and E2 levels by ELISA after acupuncture intervention,detected ovarian morphology by HE staining methods,and observed the follicular development after acupuncture intervention in PCOS rats in order to determine the efficacy of acupuncture in the treatment of PCOS ovulation disorders.(2)Using PCOS rats as a model,used Western-blot and immunohistochemical methods to detect changes in the expression levels of LC3II/I and p62 protein in ovarian granulosa cells of PCOS rats,and detected serum T,FSH,AMH,LH and E2 levels by ELISA.HE staining detected ovarian morphology to confirm the correlation between ovarian granulosa cell autophagy and PCOS follicular development,clarifed that ovarian granulosa cell autophagy affecting follicular development and promoting the occurrence and development of PCOS.Western-blot and immunohistochemical methods detected changes in the expression levels of MEG3,PI3 K,AKT,m TOR,LC3II/I and p62 proteins,ELISA detected serum T,FSH,AMH,LH and E2 levels,and HE staining detected ovarian morphology to clarify whether Lnc MEG3 mediating the PI3K/AKT/m TOR pathway to regulate ovarian granulosa cell autophagy,and affected follicle development and participates in the development of PCOS.(3)Using the PCOS rat model.After establishing the model successfully,performed acupuncture intervention for 11 days.Taken the ovarian granulosa cells of from the PCOS rats,and detected MEG3,PI3 K,AKT,m TOR,LC3II/I and p62 protein expression level by Western-blot and immunohistochemistry.;detected rat serum sex hormones(T,E2,LH,FSH,AMH)by ELISA method;detected ovarian morphology by HE staining and other methods simultaneously,observed the effect of acupuncture on the expression of Lnc MEG3 on The whole mouse and the morphology of the ovary,etc.,in order to clarify the mechanism of acupuncture treatment of PCOS ovulation disorders.Results(1)PCOS rat modeling was successful: in terms of ovarian morphology,the ovarian structure of the normal group was complete,and normal follicles could appear,and the ovaries of the model group were enlarged and cauliflower-like,no normal follicles,and the granular cells contained in the follicles were reduced and scattered;observation In the vaginal smear of rats,there were differences in the estrus cycle between the normal group and the model group.The former lasts for three to five days,while the latter did not appear.Most of them were in the preestrus stage,and a few had late estrus and estrus.Interval;in terms of overall morphology,the weight of the rats in the former group increased slowly,and only a few increased;the latter group grew rapidly,and the hormone levels were tested.The FSH,E2,LH and T and AMH of the former group were still at At the normal level,the AMH,FSH,LH,and T of the latter group maintained a growth trend,while E2 was a decline.(2)The weight loss trend of rats in the acupuncture group was higher than that of the other groups(normal group,model group,western medicine group,sham acupuncture group)(P<0.05).(3)The levels of sex hormones LH,FSH,E2 in the acupuncture group(compared to the model group,sham acupuncture group,and western medicine group)were more likely to be in the normal group(P<0.05),but the AHM level in the acupuncture group Compared with other groups(model group,sham acupuncture group,normal group,western medicine group),the difference was not big(P>0.05).(4)The ovaries of the rats in the model group had obvious cystic changes,and the number of normal follicles was very small.The ovaries of the acupuncture group,normal group,sham acupuncture group,and western medicine group could have 1-2 normal follicles and could ovulate normally.(5)P62,LC3II/I,MEG3,PI3 K,Art,and m TOR were highly expressed in granular cells in the model group,and P62,LC3II/I,MEG3,PI3 K,Art,and m TOR were low in granular cells in the normal group.After acupuncture or sham acupuncture and western medicine group intervention,the expression of autophagy factors P62 and LC3II/I in rat granulosa cells decreased and there were differences between the three intervention methods.The acupuncture group tended to the normal group most.(6)The relative expression levels of MEG3,m TOR,PI3 K,Akt,LC3II/I,and p62 proteins in rat ovarian granulosa cells in the model group were significantly higher,while the expression levels of MEG3,m TOR,PI3 K,Akt,LC3II/I,and p62 proteins were in the normal group.The expression of ovarian granulosa cells in rats was relatively low.After acupuncture or sham acupuncture intervention,the expression of ovarian granule particles MEG3,m TOR,PI3 K,Akt,LC3II/I,and p62 all decreased..Conclusion:Acupuncture regulates the expression of Lnc MEG3 and mediates the PI3K/AKT/m TOR pathway to regulate ovarian granulosa cell autophagy and participates in the occurrence and development of PCOS ovulation disorders.This may be one of the mechanisms of acupuncture treatment of PCOS. |
PDF Full Text Request