Role Of P2X₂Receptor Increased Expression On Overactive Bladder Of Female Patiens: A Preliminary Study

Background and objective:Overactive bladder （OAB） is one of the common diseases in urology, especially infemale patients. The Standardisation Subcommittee of the International Continence Society（ICS） now recognizes OAB as a "symptom syndrome suggestive of lower urinary tractdysfunction." It is specifically defined as "urgency, with or without urge incontinence, usuallywith frequency and nocturia." Up to now, the cause and pathogenesis of OAB are still unclear.Recent studies have shown that bladder hyperesthesia and detrusor overactivity may be animportant reason of lower urinary tract symptoms in OAB patients. Urodynamic study is animportant means of diagnosis of voiding dysfunction, however, whether it is necessary forOAB patients is still controversial, some scholars believe that the patients according toclinical symptoms combined with routine examination such as urine analysis can diagnose,invasive urodynamic study is unnecessary. In OAB guideline of China, the urodynamicstudies are also listed in optional items. Urodynamic study about OAB patients is less and theincidence of bladder hyperesthesia and detrusor overactivity are still not clear.In recent years, more and more attentions arebeing paid to the role of purinergic nervesignals to ATP in the regulation of bladder function. P2X receptors are one of the importanttarget molecules of ATP, seven subtypes have been found till now. Most studies on the P2Xreceptors are limited to animals, human beings rarely reported. O’Reilly and Tempest’studieshave shown the changes of P2X receptor expression in bladder tissue of bladder outletobstruction and interstitial cystitis patients. As an important molecular involved in bladdersensation, whether it is involved in the occurrence of OAB has not been reported.Material and Methods:Seventy female OAB patients and30normal volunteers participated in the study. Firstly,urodynamic studies were used to assess the bladder function of OAB patients and normalcontrol. Then the patients with bladder hyperesthesia and detrusor overactivity were selectedand bladder tissues of these patients were harvested through cystoscope. At last, Real time-PCR, immunofluorescence staining and immunohistochemical staining were used todetect the mRNA and protein expression of P2X₂receptors.Results:1．The results of urinary flowmetry showed that Qmax had no significant differencebetween the two groups （P>0.05）. While Qave and Vv of experimental group weresignificantly smaller than those of control group （P <0.05）. According to pressure-flow study,VFD, VSD, Vur, MC and BC of experimental group were significantly smaller than those ofcontrol group （P <0.01）, PdetQmax of experimental group were higher than that of controlgroup, Bladder hyperesthesia incidence of experimental group （80.9%） was significantlyhigher than that of control group （7.4%）（P <0.05）. DO incidence of experimental group（23.5%） was significantly higher than that of control group （3.3%）（P <0.01）.2．Real time-PCR results showed that P2X₂mRNA expression levels of bladder trigoneand dome region of experimental group were higher than that of the control group （P <0.01）,but there is no difference in ladder sidewall between the two groups.3．Immunofluorescence staining showed that the P2X₂receptor was detected in theepithelial cells of bladder mucosa layer. It was distributed at the cytoplasmcytoplasm incontrol group while at the nuclear in experimental group.4．Immunohistochemical staining showed that: the total express level of P2X₂receptor inthe bladder tissue of experimental group was significantly higher than that of control group （P<0.05）, and P2X₂receptors were scattered expressed in interstitial cells of bladder submucosaand smooth muscle cells of experimental group.Conclusion:1．The urodynamic characteristics of OAB patients were bladder hyperesthesia, bladdercapacity decreases, low compliance and detrusor overactivity. It is an important examinationmethod for individualized treatment of female OAB patient.2．The total express level of P2X₂receptor in the bladder tissue of experimental groupwas significantly higher than that of control group suggesting that the P2X₂receptorupregulation may be involved in the occurrence of OAB.