基于PI3K/Akt通路探讨灵泽片对前列腺增生大鼠的干预机制

The mechanism of Lingze tablets on prostate hyperplasia rats based on PI3K/Akt pathway

目的基于PI3K/Akt通路探讨灵泽片对良性前列腺增生大鼠的干预机制。方法将40只SPF级SD大鼠随机等分为正常组、模型组、非那雄胺组、灵泽片低剂量组、灵泽片高剂量组。除正常组外,余各组大鼠采用非去势丙酸睾酮诱导法建立前列腺增生大鼠模型。造模结束后,正常组及模型组选用生理盐水,非那雄胺组、灵泽片低剂量组及灵泽片高剂量组分别选用相应药物,连续灌胃给药28天。灌胃结束后处死大鼠,取前列腺组织,观察各组大鼠前列腺指数、组织结构及PI3K/Akt信号通路相关蛋白的变化。结果与正常组比较,模型组大鼠前列腺组织增生明显,前列腺指数及PI3K、Akt、Bcl-2蛋白表达水平上升(P<0.01),Bax蛋白表达水平下降(P<0.01)。与模型组比较,非那雄胺组、灵泽片高剂量组大鼠前列腺指数及Bcl-2、PI3K及Akt蛋白表达水平下降(P<0.01),Bax蛋白表达水平上升(P<0.01);灵泽片低剂量组前列腺指数及PI3K、Akt、Bcl-2蛋白表达降低,Bax蛋白表达增高,但仅前列腺指数与Akt蛋白表达水平差异有统计学意义(P<0.05)。结论灵泽片可能通过负向调控PI3K/Akt信号通路,下调PI3K、Akt及Bcl-2蛋白表达水平,上调Bax蛋白表达水平,抑制细胞增殖和促进细胞凋亡,从而发挥对BPH的治疗作用;高剂量使用灵泽片时治疗效果更佳。

tObjective To investigate the intervention mechanism of Lingze Tablet on benign prostatic hyperplasia(BPH)rats based on the PI3K/Akt pathway.Methods Forty SPF-grade SD rats were randomly divided into normal,model,finasteride,low-dose,and high-dose groups.Except for the normal group,all rats in the remaining groups were induced with non-castrated testosterone propionate to create a rat model of prostate hyperplasia.After the modeling,the normal and model groups were given saline,while the finasteride,low-dose,and high-dose groups were given the corresponding drugs by gavage for 28 days.After gavage,the rats were sacrificed,and the prostate tissues were collected to observe the changes in the prostate index,tissue structure,and PI3K/Akt signaling pathway-related proteins in each group.Results Compared with the normal group,the rats in the model group showed significant hyperplasia of prostate tissue,increased prostate index,and expression levels of PI3K,Akt,and Bcl-2 proteins(P<0.01),and decreased expression levels of Bax protein(P<0.01).Compared with the model group,the prostate index and Bcl-2,PI3K,and Akt protein expression levels decreased(P<0.01),and Bax protein expression levels increased(P<0.01)in the finasteride and Lingze tablet high-dose groups.The prostate index and PI3K,Akt,and Bcl-2 protein expression decreased,and Bax protein expression increased in the Lingze tablet lowdose group.However,only the differences in the prostate index and Akt protein expression levels were statistically significant(P<0.05).Conclusion Lingze Tablet can negatively regulate the PI3K/Akt signaling pathway,down-regulate PI3K,Akt,and Bcl-2 protein expression levels,and up-regulate Bax protein expression levels,inhibiting cell proliferation and promoting apoptosis,thus exerting therapeutic effects on BPH.The therapeutic effect is better when using Lingze Tablet at high doses.