MNU诱导大鼠膀胱癌基底膜病变与LN的相关性

Correlation between MNU-induced Bladder Membrane Damage in Rat Bladder and LN

目的观察N-甲基亚硝基脲(MNU)在诱导SD雌性大鼠膀胱癌的过程中,膀胱基底膜的病变情况与层粘连蛋白(Laminin,LN)的相关性。方法MNU 2 mg/次进行大鼠膀胱灌注,间隔2周,共4次;然后继续正常喂养6周,14周为诱癌终点。分别在MNU灌注后1周及诱癌终点14周用病理学检测观察膀胱粘膜变化情况;免疫组织化学检测基底膜中LN的表达情况,分析其相关性。结果病理结果显示:MNU灌注后膀胱粘膜经过了炎症性改变、异型增生、原位癌、浸润性癌等过程;免疫组化显示基底膜连续、完整的结构,出现断裂、缺损,最后视野下为散在碎片,无基底膜形态;LN在MNU诱导大鼠膀胱癌形成过程中随着基底膜的破坏逐渐减少,缺失;LN在基底膜中的表达在正常膀胱组织与膀胱癌之间存在差异性统计意义(χ2=25.37;P<0.01)。结论膀胱癌的发生、发展与基底膜的破坏密切相关,且LN的缺失是基底膜破坏导致膀胱癌的因素之一。

Objective To observe the correlation between the pathological changes of bladder basement membrane and laminin(LN)in N-methylnitrosourea(MNU)in the induction of bladder cancer in SD female rats.Methods Rats were intravesically infused with MNU 2 mg/time,2 weeks apart for 4 times.Then normal feeding was continued for 6 weeks,and 14 weeks was the end point of cancer induction.The changes of bladder mucosa were observed by pathological examination at 1 week after MNU perfusion and 14 weeks after induction of cancer.Immunohistochemistry was used to detect the expression of LN in the basement membrane and analyze its correlation.Results The pathological results showed that the bladder mucosa after MNU infusion had undergone inflammatory changes,dysplasia,carcinoma in situ,invasive carcinoma,etc.Immunohistochemistry showed continuous and intact structure of the basement membrane,and fractures and defects appeared.There are scattered fragments and no basement membrane morphology;LN is gradually reduced with the destruction of basement membrane during MNU-induced bladder cancer formation;the expression of LN in the basement membrane is different between normal bladder tissue and bladder cancer.Statistical significance(χ2=25.37;P<0.01).Conclusion The occurrence and development of bladder cancer is closely related to the destruction of basement membrane,and the loss of LN is one of the factors leading to bladder cancer caused by destruction of basement membrane.