如意金黄贴对前列腺增生模型大鼠P38、JNK2、NF-кBP65和STAT3蛋白的影响

Ruyi Jinhuang Plaster suppresses BPH by reducing the expressions of P38,JNK2,NF-кBP65 and STAT3 in the prostate tissue of rats

目的:探讨如意金黄贴(RJP)对丙酸睾酮所致大鼠良性前列腺增生(BPH)的作用及机制。方法:雄性SD大鼠48只,随机分为6组,即对照组、模型组、保列治组、RJP高剂量组、RJP中剂量组、RJP低剂量组,每组8只。对照组注射生理盐水0. 5 ml/kg,其余各实验组皮下注射丙酸睾酮10 mg/kg,每天1次,连续30 d,诱导建立BPH模型。于造模第1天起给予药物干预,保列治组灌胃给药保列治(4. 5 mg/kg),RJP高、中、低剂量组大鼠背部脱毛区贴42. 0、21. 0、10. 5 cm2/kg的药膏,对照组和模型组背部脱毛区贴基质贴,每天给药1次,连续30 d。实验结束取前列腺、精囊腺和包皮腺; HE染色观察前列腺病理组织形态学,计算前列腺间质、上皮和腺腔面积比; Western印迹分析P38、NF-кBP65、、STAT3、和JNK2的蛋白表达。结果:与模型组比较,RJP高剂量组可降低前列腺上皮细胞增生,下调上皮细胞面积比,上调腺腔面积比(P <0. 05); RJP高剂量组可明显降低前列腺组织中P38、pP38、NF-кBP65、p-NF-кBP65、STAT3、p-STAT3、JNK2的表达,RJP中剂量组可减少大鼠前列腺组织中JNK2和NF-кBP65的表达,上调p-JNK表达(P <0. 05),RJP低剂量组可明显减少大鼠前列腺组织中JNK2的表达而上调p-JNK表达(P <0. 05)。结论:RJP可通过抑制P38、p-P38、NF-кBP65、p-NF-кBP65、STAT3、p-STAT3、JNK2的表达、或上调p-JNK表达拮抗大鼠前列腺增生。

Objective: To investigate the effect of Ruyi Jinhuang Plaster( RJP) on testosterone propionate-induced BPH in the rat model and its action mechanisms. Methods: Forty-eight SD male rats were randomly divided into six groups of equal number: normal control,BPH model control,finasteride,and high-,medium-and low-dose RJP. The BPH model was made in the latter five groups by hypodermic injection of testosterone propionate. From the first day of modeling,the rats of the normal control and BPH model control groups were treated with blank plasters and those of the high-,medium-and low-dose RJP groups with RJPs at 42. 0,21. 0 and 10. 5 cm^2/kg applied to the dehaired area of the back,and those of the finasteride group by gavage of finasteride at 4. 5 mg/kg,all once a day for 30 successive days. Then the prostates of the animals were harvested for observation of histopathological changes by HE staining,measurement of the areas of interstitial and epithelial cells and prostatic glandular cavity,and determination of the expressions of P38,JNK2,NF-кBP65 and STAT3 proteins in the prostate tissue by Western blot. Results: Compared with the BPH model controls,the high-dose RJP group showed significantly decreased proliferation and area proportion of prostatic epithelial cells( P <0. 05),increased area proportion of the prostatic glandular cavity( P < 0. 05),and reduced expressions of P38,p-P38,NF-кBP65,P-NF-кBP65,STAT3,P-STAT3 and JNK2 in the prostate tissue( P < 0. 05); the medium-dose RJP group exhibited markedly downregulated expressions of JNK2 and NF-кBP65( P < 0. 05) but an up-regulated level of p-JNK( P < 0. 05); while the low-dose RJP group displayed a remarkably reduced expression of JNK2( P < 0. 05) but an elevated level of p-JNK( P < 0. 05). Conclusion:RJP suppresses BPH in the model rat by down-regulating the expressions of P38,p-P38,NF-кBP65,P-NF-кBP65,STAT3,P-STAT3 and JNK2 or up-regulating that of p-JNK in the prostate tissue.