| Chronic pelvic pain(SPID-CPP)is a common public health problem in women,which seriously interferes with the daily life and work of patients.At present,nonsteroidal drugs and opioids are commonly used as treatment methods for this disease,but there are still drug addiction and obvious gastrointestinal reactions,and the clinical use is limited.Therefore,it has become a hot research topic to explore the trade-off medicine to solve the pain and injury of women.Although the pathogenesis of chronic pelvic pain is still unclear,recent studies have shown that chronic pelvic pain is closely related to "inflammatory microenvironment";Our team’s previous literature research found that blood stasis syndrome is the core pathogenesis of chronic pelvic pain in the sequelae of pelvic inflammatory disease;Huayu San jie enema liquid is a listed drug for treating chronic pelvic pain of SPID.Many clinical studies have shown that it has a good effect on analgesia.Based on the above conclusions,we propose the hypothesis that "whether the traditional Chinese medicine can improve the inflammatory microenvironment by inhibiting the immune inflammatory effect and thus achieve analgesic effect".Therefore,the research is divided into:①Clinical research;②Network pharmacology;③The experiment research three modules.Objectives1.Clinical study:To evaluate the clinical efficacy of the traditional Chinese medicine for promoting blood circulation and stasis in the treatment of SPID-CPP and explore the related factors of pain in the pain degree of SPID-CPP,and provide evidence-based evidence for clinical application.2.Network pharmacology:Based on the network pharmacology,the molecular regulation mechanism of Huayu San jie clysis solution in the treatment of SPID-CPP is predicted.The possible target and pathway of the treatment of SPID-CPP are explored preliminarily,which provides the thinking and reference for the experimental research of Chinese medicine to prevent and control SPID-CPP.3.experimental study:the analgesic and anti-inflammatory effects of "activating blood and removing stasis" were observed by using the model of chronic pelvic pain rats with pelvic inflammatory disease sequelae,and the possible mechanism of online pharmacology excavation was verified.Methods1.clinical research:115 patients with SPID-CPP from 11 hospitals were included in the clinical study of multicenter,single arm,prospective and open world.The patients were given three menstrual cycles of enema with activating blood circulation and removing stasis.The general data of patients were collected.VAS score,local signs score,TCM syndrome score and SF-36 score before and after treatment were collected,To explore the related factors and efficacy of different pain levels in patients with SPID-CPP.2.Network pharmacology:the active components and target genes of Huayu San jie clysis solution were inquired by tcmsp database and related literature,and the name was standardized by uniport database;Then,the relevant targets of SPID-CPP were obtained by genecards database,and the mapping set of TCM and disease targets was made by R language;Then,the intersection target is submitted to string platform,and the protein interaction network is obtained and the network topology analysis is carried out by using cyberscape 3.7.2,and the important targets are selected;Finally,go annotation and KEGG enrichment analysis are carried out through Davis database.3.experimental study:the animal model of SPID-CPP rats was established.The group was set up as blank group(Control),model group(Model),low dose group of traditional Chinese medicine(HYSJ-L,2.25 ml/(kg·d),about 0.5 times of clinical daily dose,medium dose group of traditional Chinese medicine(HYSJ-M,4.5 ml/(kg·d),high dose group of traditional Chinese medicine(HYSJ-H,9.0 ml/(kg·d),About twice the daily dose of clinical.The enema was started on the 21st day after the model was established,and the analgesic and anti-inflammatory effects of SPID CPP were observed in all groups of "Huayu San jieenema liquid".The local tissues were sectioned and analyzed by HE staining.The immunohistochemistry,Western blot,RT-PCR and other techniques were used to detect the relevant immunoinflammatory factors and NF in the tissues of the uterus and spinal dorsal root ganglion NF-κB.Results1.Clinical study:① the pain level of SPID-CPP patients may be related to age,number of pregnancy and childbirth,recurrence PID frequency and other factors.②The results showed that the VAS score,local sign score,TCM syndrome score and SF-36 concise health score were significantly lower in patients with SPID-CPP and the simple health score of SF-36,which was significantly different from that before treatment(P<0.05).2.Network pharmacology:15 Chinese herbs in Huayu San jieclysis liquid contain 58 active components,which play a therapeutic role in SPID CPP at 55 intersection targets,among which the important targets are Rela(p65),TNF-α、MIP-2 and other genes are mainly enriched in NF-κB(NF-κB signaling path).3.experimental study:SPID CPP can cause TNF in rats TNF-α、NF-κB,MIP-2 level increased,and Huayu San knot enema solution could effectively reduce TNF in SPID CPP rats TNF-α、NF-κB、MIP-2 can effectively improve the chronic pelvic pain in rats with pelvic inflammatory disease sequelae.Conclusions1.Clinical study:the pain degree of SPID-CPP may be related to the patient’s age and PID infection frequency.Huayu San jie enema liquid has a certain therapeutic effect on SPID-CPP,which can effectively improve the patients’ pelvic pain,local signs of pelvis,TCM syndromes and quality of life.2.Network pharmacology:Huayu San jieenema liquid can treat SPID-CPP through multi-component,multi-target and multi-channel,which may be through TNF-α/NF-κB/MIP-2 signaling pathway plays a therapeutic role.3.Experimental study:"Huoxue Huayu" can inhibit inflammatory response,regulate immune function and down regulate NF-κB pathway may be one of the molecular mechanisms of its analgesic effect. |
