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目的:探讨磷脂酰肌醇3激酶/蛋白激酶B(PI3K/PKB或PI3K/AKT)信号通路抑制剂对前列腺增生的影响及机制。方法:选用鼠龄12周的雄性SD大鼠48只,随机分为4组:假手术对照组;BPH模型组;LY294002 50 mg组和LY294002 100 mg组,每组12只。大鼠去势后肌注丙酸睾酮10 mg/(kg.d)连续30 d建模,LY294002 50 mg组和100 mg组同时肌注LY294002 50 mg/kg和100 mg/kg,隔日1次。给药30 d后,切除各组大鼠前列腺组织,称取前列腺重量,切片观察前列腺组织细胞结构变化。免疫组化法检测K i-67、凋亡相关蛋白Bc l-2与Bax的表达情况;核酸末端原位标记法(TUNEL)检测细胞凋亡情况。结果:各组大鼠前列腺湿重(mg)和前列腺指数:假手术对照组:551±10.8,1.61±0.05;模型组:687±13.8,2.15±0.12;LY294002 50 mg组:623±23.5,1.95±0.11,与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:561±12.6,1.71±0.18,与模型组相比,差异具有极显著性(P<0.01)。凋亡相关蛋白Bax与Bc l-2的表达:假手术对照组:16.7%,16.7%;模型组:16.7%,58.3%;LY294002 50 mg组:33.3%,33.3%,与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:50.0%,25.0%,与模型组相比,差异极有显著性(P<0.01)。增殖和凋亡指数(%):假手术对照组:上皮组织14.2±6.4,6.5±1.8,间质组织7.6±2.6,2.5±0.3;模型组:上皮组织50.9±12.8,2.7±1.4,间质组织16.5±5.7,1.3±0.8;LY294002 50 mg组:上皮组织32.0±13.8,6.2±2.5,间质组织12.1±3.8,1.6±1.1;与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:上皮组织17.8±14.7,7.4±3.6,间质组织9.5±3.4,2.2±1.3;与模型组相比,差异有显著性(P<0.05)或极显著性(P<0.01)。结论:前列腺增生动物模型前列腺细胞增殖增加和凋亡的相对减少参与了BPH的发生发展过程。PI3K/AKT介导的信号通路在前列腺增生的发生发展过程中起重要作用,阻断PI3K/AKT信号通路具有抑制前列腺增生的作用。
Objective: To investigate the effect of phosphatidylinositol 3 kinase / protein kinase B (PI3K / PKB or PI3K / AKT) signaling pathway inhibitor on prostatic hyperplasia and its mechanism. Methods: Forty eight male Sprague-Dawley rats of 12 weeks old were randomly divided into 4 groups: sham operation control group, BPH model group, LY294002 50 mg group and LY294002 100 mg group, 12 rats in each group. Rats were intramuscularly injected with 10 mg / (kg.d) of testosterone for 30 days after modeling. LY294002 50 mg and 100 mg groups were intramuscularly injected with LY294002 50 mg / kg and 100 mg / kg once every other day. After administration for 30 days, the prostate tissue of each group was excised, the weight of the prostate was weighed, and the changes of the cell structure of the prostate tissue were observed. Immunohistochemistry was used to detect the expression of K i-67 and Bcl-2 and Bax, and the apoptosis was detected by TUNEL. Results: The wet weight of the prostate (mg) and the prostatic index in each group were sham operation control group: 551 ± 10.8 and 1.61 ± 0.05; model group: 687 ± 13.8 and 2.15 ± 0.12; LY294002 50 mg group: 623 ± 23.5 and 1.95 ± 0.11, compared with the model group, the difference was significant (P <0.05); LY294002 100 mg group: 561 ± 12.6,1.71 ± 0.18, compared with the model group, the difference was significant (P <0.01). Compared with model group, the expression of Bax and Bcl-2 in Bax and Bcl-2 in sham operation group was 16.7% and 16.7% in sham operation group, 16.7% and 58.3% in model group, 33.3% and 33.3% in LY294002 50 mg group, (P <0.05). Compared with the model group, the difference was significant (P <0.01) in LY294002 100 mg group: 50.0% and 25.0% respectively. Proliferation and apoptosis index (%): sham operation control group: epithelial tissue 14.2 ± 6.4,6.5 ± 1.8, interstitial tissue 7.6 ± 2.6,2.5 ± 0.3; model group: epithelial tissue 50.9 ± 12.8,2.7 ± 1.4, 16.5 ± 5.7 and 1.3 ± 0.8 in the LY294002 group, 32.0 ± 13.8 and 6.2 ± 2.5 in the epithelial tissue and 12.1 ± 3.8 and 1.6 ± 1.1 in the interstitial tissue, respectively. Compared with the model group, the difference was significant (P <0.05) ; LY294002 100 mg group: epithelial tissue 17.8 ± 14.7,7.4 ± 3.6, interstitial tissue 9.5 ± 3.4,2.2 ± 1.3; compared with the model group, the difference was significant (P <0.05) or very significant (P <0.01 ). Conclusion: Prostatic hyperplasia model prostatic hyperplasia and apoptosis relative decrease participate in the development of BPH. PI3K / AKT-mediated signaling plays an important role in the occurrence and development of benign prostatic hyperplasia, blocking the PI3K / AKT signaling pathway can inhibit the proliferation of benign prostatic hyperplasia.