Intracorporal injection of hSlo cDNA in rats produces physiologically relevant alterations in penile function
Intracorporal injection of hSlo cDNA in rats produces physiologically relevant alterations in penile function
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DOI：
10.1152/ajpheart.1998.275.2.h600
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发表时间：
1998-08-01
影响因子：
4.8
通讯作者：
Geliebter, J
中科院分区：
文献类型：
--
作者：
Christ, GJ;Rehman, J;Geliebter, J
Ca 2+敏感性K+通道（maxi-K+）是体平滑肌张力的重要调节剂。这些研究的目的是双重的：I）确定用编码人平滑肌maxi-K+通道的hSlo cDNA在体内转染体平滑肌细胞的可行性，以及21确定maxi-K+通道的转染是否会影响体内大鼠模型中对海绵体神经刺激的生理反应。在10周龄大鼠脑内显微注射pCMV β/Lac Z.DNA，12只注射动物中有10只在注射后75天内出现显著的β-半乳糖苷酶活性掺入和表达。此外，海绵体神经的电刺激显示，相对于在年龄匹配的对照动物（N = 12）中获得的反应，海绵体内注射裸pcDNA/hSlo DNA与在所有水平的电流刺激下海绵体内压力反应的平均幅度的统计学显著升高相关（范围0.5-10 mA）在注射后1个月（N = 5）和2个月（N = 8）。此外，在注射后3个月（N = 2）和4个月（N = 2）进行了定性相似的观察。这些数据表明，裸露的hSlo DNA很容易掺入到身体平滑肌中，此外，在体内的身体平滑肌细胞中表达持续至少2个月。最后，表达后，hSlo能够可测量地改变神经刺激的阴茎勃起。总之，这些数据为基因治疗在治疗勃起功能障碍中的潜在效用提供了令人信服的证据。
The Ca2+-sensitive K+ channel (maxi-K+) is an important modulator of corporal smooth muscle tone. The goal of these studies was twofold: I) to determine the feasibility of transfecting corporal smooth muscle cells in vivo with the hSlo cDNA, which encodes for the human smooth muscle maxi-K+ channel, and 21 to determine whether transfection of the maxi-K+ channel would affect the physiological response to cavernous nerve stimulation in a rat model in vivo. Intracorporal microinjection of pCMV beta/Lac Z.DNA in 10-wk-old rats resulted in significant incorporation and expression of beta-galactosidase activity in 10 of 12 injected animals for up to 75 days postinjection. Moreover, electrical stimulation of the cavernous nerve revealed that, relative to the responses obtained in age-matched control animals (N = 12), intracavernous injection of naked pcDNA/hSlo DNA was associated with a statistically significant elevation in the mean amplitude of the intracavernous pressure response at all levels of current stimulation (range 0.5-10 mA) at both 1 mo (N = 5) and 2 mo (N = 8) postinjection. Furthermore, qualitatively similar observations were made at 3 mo (N = 2) and 4 mo (N = 2) postinjection. These data indicate that naked hSlo DNA is quite easily incorporated into corporal smooth muscle and, furthermore, that expression is sustained for at least 2 mo in corporal smooth muscle cells in vivo. Finally, after expression, hSlo is capable of measurably altering nerve-stimulated penile erection. Taken together, these data provide compelling evidence for the potential utility of gene therapy in the treatment of erectile dysfunction.