脱特罗定持续干扰胆碱能神经支配时大鼠良性增生前列腺腺上皮细胞的影响

Changes of rat＇ s benign hyperplasia prostate glandular epithelium cells after interfering cholinergic innervations by drug

目的观察脱特罗定持续干扰胆碱能神经支配对大鼠良性增生前列腺腺上皮的影响。方法将29周龄雄性自发性高血压（SHR）大鼠42只，分为实验组18只，对照组18只，正常对照组6只。实验组每天2次脱特罗定（3．5mg/kg体质量，溶解于1．0ml生理盐水）灌胃给药，对照组每天2次胃内灌人等量的生理盐水，正常对照组不做任何处理。每12周处死一批大鼠，比较各组SHR大鼠前列腺腹侧叶大体形态、湿重／体质量比值、干重／湿重比值，组织切片光镜、透射电镜下观察，免疫组织化学LC3—Ⅱ染色等。结果各阶段实验组SHR大鼠前列腺腹侧叶大体形态与对照组差异不明显，两组大鼠前列腺腹侧叶湿重／体质量比值随周龄均进行性升高，各阶段两者差异均无统计学意义（P〉0．05）；对照组大鼠前列腺腹侧叶干重／湿重比值随周龄进行性升高，但实验组升高趋势不明显，41周龄后两组差异有统计学意义（P〈0．01）；光镜下观察，对照组大鼠前列腺腺上皮细胞继续呈现良性增生状态且进行性明显，而实验组大鼠前列腺腺上皮细胞逐渐出现萎缩性改变，41周龄后两组差异较为明显；电镜下观察，对照组前列腺腺上皮细胞呈现随周龄进行性明显的细胞增生和分泌功能亢进，腺细胞胞质内自噬体、自噬前体和自噬溶酶体结构众多；而实验组腺上皮细胞增生表现和胞质内自噬体结构随大鼠周龄的增加而逐渐下降，41周龄后两组差异有统计学意义（P〈0．01）；典型的细胞凋亡现象在实验组和对照组各阶段差异均不明显；免疫组织化学实验发现，实验组大鼠前列腺腺上皮细胞胞质LC3-Ⅱ／LC3-Ⅰ阳性染色较同周龄对照组大鼠显著下降，其差异亦随大鼠周龄的延长而更明显，41周龄后差异有统计学意义（P〈0．01）。实验组大鼠与正常对照组比较，上述差异均无统计学意义（P〉0．05）。结论药物持续干扰前列腺胆碱能神经支配后，大鼠良性增生前列腺腺上皮细胞逐渐出现萎缩改变，该病理过程与腺上皮细胞内自噬活性的显著下降可能有重要关系。

Objective To investigate the changes of rats＇ benign hyperplasia prostate glandular epithelium cells after continuing blockade the cholinergic innervation by drug. Methods All 42 male spontaneous hypertension rats （SHR, a spontaneous BPH animal model, 29 weeks old） were divided into experiment group （EG） , control group （CG） and normal control （NC）. EG were intragastric administered with Tolterodine （3.5 mg/kg, bid） , CG were intragastrie administered with equivalent physiological saline. Rats were sacrificed in batches every 12 weeks, the changes of the prostate gross morphology, ratio of ventral prostate lobe wet weight and body weight （wet/body） , ratio of ventral prostate lobe dry weight and wet weight （wet/dry） , histology, ultra-structure and LC3-Ⅱ ＆ LC3-Ⅰ expression were observed. Results The gross morphological changes and the increase of wet/body ratio of EG rats＇ prostate were similar to CG in every stage. The wet/body ratio of two group increased with rats＇ age, but EG were significantly smaller than CG after 41 weeks. The proliferation of prostate glandular epithelium cell in EG were stopped while in CG were continuing. The number of autophagosome was increased with age in CG glandular cell cytoplasm, while in EG, the number of autophagosome was decreased with age. The immunohistrochemistry staining of LC3-Ⅰ progressively attenuated and LC3-Ⅱ staining progressively reinforced with the rat＇ s age in CG, but in EG, the situation were conversed. All these index between CG and NC, had no statistical difference. Conclusion The benign hyperplasia of rats＇ prostate glandular epithelium cells have been reversed after blockade the cholinergic innervation by drug, the significantly inactivation of autophagy may play an impor- tant role.