Cantharidin Causes Acute Cystitis In Mice And Explores Related Mechanisms

To explore the pathological expression and related mechanism of cantharidin(CTD)in acute cystitis induced by intragastric administration of 1/2(median lethal dose,LD50).Through exploring the basic biological mechanism of cantharidin induced acute cystitis,we can reduce or even eliminate cantharidin bladder toxicity and expand the clinical use of cantharidin.MethodsBalb/c mice were fed for 1 weeks,and they were divided into blank group and cantharidin administration for 1?14 day group.The drug groups were administered with cantharidin 1/2 LD50 for different days,while the blank group were given the same amount of 0.5%sodium carboxymethylcellulose(CMCNa).After the last administration,The histopathological changes of the bladder in mice were detected by hematoxylin-eosin(HE)staining and the pathological changes of the bladder were observed 1 to 14 days after the administration of cantharidin.The bladder pathology was semi-quantitatively analyzed.Western blot was used to detect the expression of inflammation-related signal transduction pathway and apoptosis-related signal transduction pathway in the bladder tissue of cantharidin administered 1 day mice,Semi-quantitative analysis and statistical calculation based on protein gray value were done.ResultsThe bladder HE staining results showed that:compared with the blank group,cantharidin administered 1 days group,namely 3 h after administration,acute cystitis can be produced in mice,manifested as mucous layer thickening and edema,severe mucosal epithelial desquamation,epithelial hyperplasia,mucosa bleeding and other pathological changes.In conclusion,cantharidin administered 1,3,8,9,10,11 and 12 days groups had obvious pathological changes in bladder tissue,mainly manifested as mucosal epithelial denudation,mucosal epithelial hyperplasia,lamina propria edema or hemorrhage and mucosal inflammatory cell infiltration.Body had a certain ability to repair bladder damage induced by cantharidin in the first 7 days administration of cantharidin.In the 8 to 14 days,the bladder showed an irreversible and gradual aggravating inflammatory lesion.The results of Western blot showed that the expression of p-Akt and Akt protein in bladder tissue of mice in cantharidin administered 1 day group was significantly higher than that in control group(P<0.01),while the protein expression levels of p-I?B?,I?B?,NF-p65 increased(P<0.01);There was no significant difference in the total amount of NF-?B p65 protein(P>0.05).The protein levels of Bax,Bcl-2,Pro-caspase3 had no significant difference(P>0.05).ConclusionCantharidin administered 3 h can cause acute cystitis in mice.And there was a certain ability to repair the bladder injury caused by cantharidin in the first 7 days of the administration,but in the 8 to 14 days after administration the bladder showed irreversible and gradually increased inflammatory lesions.Activation of the serine/threonine kinase(Akt)signaling pathway and the nuclear factor kappa B(NF-?B)signaling pathway are associated with acute cystitis caused by cantharidin.No acute cystitis caused by cantharidin 1 day group was found to be associated with apoptosis of bladder cells.