胶球藻多糖对老年大鼠前列腺增生的抑制作用及作用机制

Inhibitory effect of cocoomyxa gloeobotrydifomis on benign prostate hyperplasia in aged rats and its action mechanism

目的:探讨胶球藻多糖(CGD)对老年大鼠前列腺增生是否有对抗作用及其作用机制。方法:选用21月龄30只健康雄性SD大鼠,采用随机数字法均分为3组:老龄大鼠对照组;CGD低剂量组[50 mg/(kg.d)];CGD高剂量组[100 mg/(kg.d)];另设青年大鼠对照组(3月龄)。采用食物咀嚼法给药,连续给药3个月。给药3个月后,切除各组大鼠前列腺组织,称取前列腺湿重;HE染色观察前列腺组织结构的改变,Masson染色观察前列腺间质的改变,Western印迹观察各组前列腺组织磷酸化3-磷脂酰肌醇依赖性蛋白激酶(PDK1)、蛋白激酶B(PKB/Akt)和PTEN蛋白表达的改变。结果:老年大鼠前列腺湿重和前列腺指数较青年对照组明显增加,分别从(550±60)mg,1.94±0.10增加到(1 220±140)mg,2.08±0.17(P<0.01)。连续应用CGD[100 mg/(kg.d)]3个月的老年大鼠前列腺湿重和前列腺指数较老年对照组明显降低[(1 080±97)mg vs(1 220±140)mg,P<0.01;1.85±0.16 vs 2.08±0.17,P<0.05)。HE染色和Masson染色结果显示老年大鼠前列腺上皮组织和间质均较给药组大鼠厚,特别是间质增厚更明显。Western印迹结果显示老年大鼠前列腺组织磷酸化PDK1和磷酸化Akt蛋白表达较青年对照组大鼠明显增加,而磷酸化PTEN蛋白表达明显降低。CGD[50、100 mg/(kg.d)]可明显降低老年大鼠前列腺组织磷酸化PDK1和磷酸化Akt蛋白表达水平,上调磷酸化PTEN蛋白表达水平。但各组间总的PDK1、Akt和PTEN蛋白表达水平没有差异。结论:CGD能明显抑制老年大鼠的前列腺增生,这种抑制作用与下调PI3K/Akt通路有关。

Objective： To investigate the inhibitory effect of cocoomyxa gloeobotrydifomis （CGD） on benign prostate hyperplasia （BPH） in aged rats and its underlying mechanism. Methods： Thirty SD male rats aged 21 months were equally randomized to three groups, aged control, low-dose CGD and high-dose CGD, the latter two groups fed on a diet with CGD at 50 and 100 mg per kg per d for 3 months, while the aged controls on normal laboratory chow. Another 10 3-month-old male rats were included in a young control group and fed on the same diet as the aged control rats. At the end of 3 months of CGD treatment, the prostates of all the rats were harvested and weighed. The histomorphological and interstitial changes of the prostatic tissue were observed by HE staining and Masson staining, respectively. The expressions of phosphorylated phosphoinositide-dependent kinase 1 （PDK1）, phosphorylated Akt （Ser 473） and phosphorylated PTEN in the rat prostate were determined by Western blotting. Results： The wet weight and index of the prostate were significantly higher in the aged controls than in the young controls （ [ 1 220 ± 140] vs [550 ± 60] mg, P 〈0.01 ; 2.08 ± 0.17 vs 1.94 ± 0.10, P 〈 0.05）. High-dose CGD significantly inhibited the increase in the prostatic wet weight and index of the aged rats （ [ 1 080 ± 97 ] mg and 1.85 ± 0.16） as compared with the aged controls （ P 〈 0.01 and P 〈 0.05 ）. The epithelium and interstitiurn, particularly the latter, were evidently thicker in the aged control than in the CGD-treated rats. The protein levels of phosphorylated PDK1 and Akt were significantly enhanced, while that of phosphorylated PTEN remarkably down-regnlated in the aged rats as compared with the young ones. The expressions of phosphorylated PDK1 and Akt were significantly decreased, whereas that of phosphorylated PTEN markedly increased in both the low-dose and high-dose CGD groups. Conclusion： CGD can significantly inhibit BPH in aged rats through down-regulating the PI3K/Akt pathway.