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[他达拉非治疗对自发性高血压大鼠阴茎海绵体组织的影响]

[Effect of tadalafil therapy upon penile cavernous tissues in spontaneously hypertensive rats].

作者信息

Wu Zhi-Gang, Wang Wen-Lan, Cai Jian, Wu Xiu-Ling, Wu Wei, Li Xiang-Bin, Li Cheng-Di, Weng Zhi-Liang

机构信息

Department of Urology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2009 Jun 23;89(24):1717-20.

Abstract

UNLABELLED

OBJECTIVE; To observe the plasma concentration change of endothelin-1 (ET-1) and the histomorphological changes in penile cavernous body after administrating a continuous low dose of tadalafil into spontaneously hypertensive rats (SHR).

METHODS

Forty SHR rats were randomly divided into four groups of blank group, placebo group, continuous low-dose group and intermittent dose group with 10 rats in each. The animals were administrated with different doses of tadalafil via an intragastric route. To observe the plasma concentration change of ET-1 and cellular morphological changes of penile cavernous tissue in SHR after four weeks, the immunohistochemical method of SABC was employed to detect the expression of alpha-smooth muscle actin (alpha-SMA) in penile corpora cavernous of different groups.

RESULTS

The plasma levels of ET-1 were lower in continuous low dose group (12.0 +/- 1.6) and intermittent dose group (14.3 +/- 1.7) as compared with the blank (18.0 +/- 1.9) and placebo groups (17.6 +/- 2.2) (all P < 0.01). And there was significant difference between the continuous low dose and intermittent dose groups (P < 0.05). The A-value level of absorbance in alpha-SMA were significantly different with the blank (0.53 +/- 0.03) and placebo groups (0.52 +/- 0.05) (P > 0.05) and it was lower in the continuous low dose group (0.29 +/- 0.03) than the intermittent dose group (0.38 +/- 0.03) (P < 0.05). It can be observed microscopically that in blank group and placebo group: endothelial cell and vascular smooth muscle cells of penile cavernous tissue in SHR had a disorderly distribution. The disrupted continuity and integrity of endothelial cell were also found. And they improved in continuous low dose group and intermittent dose group, especially the former; it can be viewed under TEM that the endothelial cells of penile cavernous tissue in SHR had mostly reverted to normal condition in the continuous low dose group and its ultra-structure indicated that the tissue morphology improved.

CONCLUSION

A continuous low dose of tadalafil can improve the function and structure of vascular endothelium in penile cavernous body. Thus it provides rationales for a continuous low dose of PDE5 inhibitor in the treatment of erectile dysfunction.

摘要

未标注

目的:观察持续低剂量他达拉非给药后自发性高血压大鼠(SHR)血浆内皮素 -1(ET -1)浓度变化及阴茎海绵体组织形态学变化。

方法

40只SHR大鼠随机分为空白组、安慰剂组、持续低剂量组和间歇剂量组,每组10只。通过灌胃途径给予动物不同剂量的他达拉非。四周后观察SHR大鼠ET -1血浆浓度变化及阴茎海绵体组织细胞形态变化,采用SABC免疫组化法检测不同组阴茎海绵体中α -平滑肌肌动蛋白(α -SMA)的表达。

结果

持续低剂量组(12.0±1.6)和间歇剂量组(14.3±1.7)的ET -1血浆水平低于空白组(18.0±1.9)和安慰剂组(17.6±2.2)(均P<0.01)。持续低剂量组和间歇剂量组之间有显著差异(P<0.05)。α -SMA吸光度的A值水平与空白组(0.53±0.03)和安慰剂组(0.52±0.05)有显著差异(P>0.05),持续低剂量组(0.29±0.03)低于间歇剂量组(0.38±0.03)(P<0.05)。显微镜下可见,空白组和安慰剂组:SHR大鼠阴茎海绵体组织的内皮细胞和血管平滑肌细胞分布紊乱。还发现内皮细胞的连续性和完整性遭到破坏。持续低剂量组和间歇剂量组有所改善,尤其是前者;透射电镜下可见,持续低剂量组SHR大鼠阴茎海绵体组织的内皮细胞大多恢复正常状态,其超微结构表明组织形态得到改善。

结论

持续低剂量他达拉非可改善阴茎海绵体血管内皮的功能和结构。因此为持续低剂量磷酸二酯酶5抑制剂治疗勃起功能障碍提供了理论依据。

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