The Machinism Of Endothelin A Receptor In Pain Conduction In Ovarian Cancer

Background: Ovarian cancer is one of the most gynecological malignant tumors,whose incidence rate is third,only after cervical cancer and uterine body cancer.But the mortality of ovarian cancer is the first place in all kinds of gynecologic cancers,it is a serious threat to women’s lives.Because most patients with the disease were dignosed in a late stage,the prognosis is still poor so far.it is difficult to be found and diagnosed early because ovarian is hidden in the pelvic cavity and inst of specific symotom.The effects of clinical treatment are poor and ovarian cancer patients five years survival rate is low,But with the continuous development of medical diagnosis and treatment,the survival time of patients with ovarian cancer is prolonged.75%-95% of the patients in advanced stage have different degrees of cancer pain performance,so how to reduce and relieve the pain of patients with ovarian cancer has become an important part of the cancer clinical treatment.Cancer pain is a common complication of late patients with ovarian cancer,it can affect patients ’ life seriously.Therefore,cancer pain control is an important part in cancer treatment,which has been emphasized.The clinical treatment of cancer pain follow the WHO cancer ache three steps and ladders treatments plan strictly at present,the use of opioid analgesics is followed from weak to strong,from less to more.Although there are some rules to follow in the treatment,serious adverse reactions and toxic side effects are still exist,such as gastrointestinal reactions,neurotoxicity,drug abuse,etc.Due to the complexity of cancer pain and the limitation of opioid drugs,we need to find new therapeutic targets for cancer pain,the new direction to solve the problem is that we’d better to choose the low,safe,exclusive and high effective targets in the pain signal transduction mechanisms.Objective:1 To research the endothelin A receptor plays the role in cancer pain in the orthotopic implantation model of ovarian.2 To research the expression of p38 MARK in the dorsal root ganglia of the orthotopic implantation model of ovarian in mice witn injection of endothelin receptor agonists(ET)and endothelin receptor antagonist(BQ123).Method:1 Choose five week female BALB-C mices,25 g,which were randomly divided into four groups(n=10),respectively blank control group,model control group,model control group deal with ET,model control group deal with BQ123.To eastablih the orthotopic implantation model of ovarian cancer in mices.The model control group deal with ET and model control group deal with BQ123 inject ET,BQ123 into vertebral canal respectively on the 9th day,the 11 th day,the 13 th day(P<0.01).2 To erplore the neuropathic pain behaviors in model mice through measure the mechanical withdrawal threshold of the mices on the day before operation,the 7th day after operation,the 11 th day after operation,the 13 th day after operation respectively.3 Kill the mics to gain the Lumbar dorsal root Anglia on the 14 th after the operation.IHC were immunostained to detect the expression of ETAR and P38 MARK in the DRG of the orthotopic implantation model of ovarian cancer in mice.western blot were detected the expression of the tissue protein P38 MARK.Result:1 Compred with the blank control group,MWT of mices in model control group was decreased at 5-12 day after operation.Compred with the model control group,no obviously change of the MWT in the model control group(P> 0.05)deal with ET at 7th day.but mechanical hyperalgesia induced by ovarian cancer can relief in the in model control group deal with BQ123.2 Compred withith the blank control group,the numer of positive cells of ETAR and P38 MARK on DRG were increased in the model control group(P<0.01),the numer of positive cells of ETAR and P38 MARK on DRG in the model control group deal with ET was higher than the model control group(P< 0.01),the model control group,numer of positive cells of ETAR and P38 MARK was higher than the model control group deal with BQ123(P <0.01).3 Compred withith the blank control group,the expression of P38 MARK on DRG were increased in the model control group(P < 0.01),the expression of P38 MARK on DRG in the model control group deal with ET was higher than the model control group(P < 0.01),the model control group,expression of P38 MARK was higher than the model control group deal with BQ123(P<0.01).Conclusion:1 Use of ETAR antagonists can partially mitigate mechanical hyper algesia response of the ovarian cancer mices,it reveals ETAR involves in the formation of ovarian cancer pain.2 the expression of p38 MARK which in the dorsal root ganglia of the orthotopic implantation model of ovarian in mice witn injection of endothelin receptor agonists(ET)and endothelin receptor antagonist(BQ123)was changed,it speculated that ETAR pain pathways may promote the expression of p38 MARK.