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大鼠海绵体中激肽释放酶-激肽系统的年龄相关变化。

Age-related changes in kallikreins-kinins system in rat corpus cavernosum.

作者信息

Wang T, Wan Z H, Liu J H, Chen M Y, Chen R B, Yang W M, Ye Z Q

机构信息

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Int J Androl. 2011 Feb;34(1):33-40. doi: 10.1111/j.1365-2605.2010.01052.x.

Abstract

Many factors, such as nitric oxide synthase, androgen and growth factors, can regulate the tone of corpus cavernosum (CC) smooth muscle with an age-related tendency. It has been shown that the active metabolites of kallikreins-kinins system (KKS), including bradykinin, Lys-BK and Met-Lys-BK, can also relax the CC smooth muscle significantly in vitro. Our aim was to evaluate the specific association between KKS and age in rat CC. CC and thoracic aorta were isolated from rats at postnatal weeks (PW) of 2, 8, 12, 20, 30, 40 and 60, respectively. Tissue kallikrein-I (KLKI) and kinin B2 receptor (B2R) mRNA in CC and thoracic aorta were detected by real-time polymerase chain reaction (PCR). Protein expression of KLKI and B2R were determined with immunofluorescence in situ and Western blot. Real-time PCR, immunofluorescence in situ and Western blot all demonstrated that the age-related changes in expression of KLKI were similar between the CC and thoracic aorta. It significantly increased with age from PW2 to PW30, reached the peak at PW30 and then declined gradually. However, there was no statistically significant difference among PW30, PW40 and PW60. Similarly, the expression of B2R increased gradually with age reached and remained at the peak during adult stages and no significant differences were found among PW20, PW30 and PW40; then, it decreased significantly at PW60. The changes in the expression of B2R in CC and age-matched aorta were similar except that it was significantly less than that in the aorta at PW60. The expression of KLKI and B2R changed in an age-dependent pattern in rat CC and have a tendency to decline during ageing, which is of the same tendency as reported for erection capacity in ageing males and suggests why ageing is an independent predictor of ED, to some extent.

摘要

许多因素,如一氧化氮合酶、雄激素和生长因子,均可调节海绵体(CC)平滑肌张力,且呈现与年龄相关的趋势。研究表明,激肽释放酶 - 激肽系统(KKS)的活性代谢产物,包括缓激肽、赖氨酸 - 缓激肽(Lys - BK)和甲硫氨酸 - 赖氨酸 - 缓激肽(Met - Lys - BK),在体外也能显著舒张CC平滑肌。我们的目的是评估大鼠CC中KKS与年龄之间的具体关联。分别从出生后第2、8、12、20、30、40和60周(PW)的大鼠中分离出CC和胸主动脉。通过实时聚合酶链反应(PCR)检测CC和胸主动脉中组织激肽释放酶 - I(KLKI)和激肽B2受体(B2R)的mRNA。采用免疫荧光原位法和蛋白质印迹法测定KLKI和B2R的蛋白表达。实时PCR、免疫荧光原位法和蛋白质印迹法均表明,CC和胸主动脉中KLKI表达的年龄相关变化相似。从PW2到PW30,其表达随年龄显著增加,在PW30达到峰值,然后逐渐下降。然而,PW30、PW40和PW60之间无统计学显著差异。同样,B2R的表达随年龄逐渐增加,在成年阶段达到并维持在峰值,PW20、PW30和PW40之间未发现显著差异;然后,在PW60时显著下降。CC中B2R表达的变化与年龄匹配的主动脉相似,只是在PW60时显著低于主动脉中的表达。大鼠CC中KLKI和B2R的表达呈年龄依赖性变化,且在衰老过程中有下降趋势,这与老年男性勃起功能的报道趋势相同,在一定程度上提示了衰老为何是勃起功能障碍的独立预测因素。

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