Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3K/AKT/eNOS Pathway
Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3K/AKT/eNOS Pathway
复制标题
人组织激肽释放酶 1 通过抑制过度氧化应激和激活 PI3K/AKT/eNOS 通路改善链脲佐菌素诱导的糖尿病大鼠的勃起功能障碍
DOI：
10.1155/2020/6834236
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发表时间：
2020-02-29
影响因子：
--
通讯作者：
Liu, Jihong
中科院分区：
文献类型：
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作者：
Luan, Yang;Cui, Kai;Liu, Jihong
目的探讨人组织激肽释放酶1（hKLK 1）对1型糖尿病（DM-）所致大鼠勃起功能障碍的保护作用及其机制。材料和方法。采用链脲佐菌素（STZ）腹腔注射方法，建立携带hKLK 1基因的纯合转基因大鼠（TGR）和年龄匹配的野生型Sprague道利大鼠（WTR）糖尿病模型。将48周龄雄性大鼠随机分为WTR组、TGR组、糖尿病WTR组（WTDM）、糖尿病TGR组（TGDM）和TGDM + HOE 140组（TGDMH），每组8只。12周后，电刺激海绵体神经检测大鼠勃起反应，并取阴茎海绵体，检测海绵体氧化应激（OS）、细胞凋亡、纤维化及相关通路的变化。同时，初步分离海绵状平滑肌细胞（CSMC）和内皮细胞（EC），建立共培养体系，进行一系列体外验证。结果转染hKLK 1基因和年龄匹配的野生型Sprague道利大鼠（WTR），腹腔注射链脲佐菌素诱导糖尿病大鼠模型。将48周龄雄性大鼠随机分为WTR组、TGR组、糖尿病WTR组（WTDM）、糖尿病TGR组（TGDM）和TGDM + HOE 140组（TGDMH），每组8只。12周后，电刺激海绵体神经检测大鼠勃起反应，并取阴茎海绵体，检测海绵体氧化应激（OS）、细胞凋亡、纤维化及相关通路的变化。结论hKLK 1可能通过抑制组织过度OS、细胞凋亡和纤维化以及激活阴茎组织中PI 3 K/AKT/eNOS/cGMP通路，保护DM大鼠的勃起功能。此外，hKLK 1促进松弛，并防止高糖诱导的损伤CSMC介导的EC-CSMC串扰。
Objective To investigate the protective effects and mechanisms of human tissue kallikrein 1 (hKLK1) on type 1 diabetes mellitus- (DM-) induced erectile dysfunction in rats. Materials and Methods. The homozygous transgenic rats (TGR) harboring the hKLK1 gene and age-matched wild-type Sprague Dawley rats (WTR) were involved, and intraperitoneal injection of streptozotocin was utilized to induce diabetes in rats. Forty-eight-week-old male rats were randomly divided into a WTR group, TGR group, diabetic WTR group (WTDM), diabetic TGR group (TGDM), and TGDM with HOE140 group (TGDMH), with eight rats in each group. Twelve weeks later, the erectile response of all rats was detected by cavernous nerve electric stimulation, and corpus cavernosums were harvested to evaluate the levels of cavernous oxidative stress (OS), apoptosis, fibrosis, and involved pathways. Moreover, cavernous smooth muscle cells (CSMC) and endothelial cells (EC) were primarily isolated to build a coculture system for a series of in vitro verification. Results The hKLK1 gene and age-matched wild-type Sprague Dawley rats (WTR) were involved, and intraperitoneal injection of streptozotocin was utilized to induce diabetes in rats. Forty-eight-week-old male rats were randomly divided into a WTR group, TGR group, diabetic WTR group (WTDM), diabetic TGR group (TGDM), and TGDM with HOE140 group (TGDMH), with eight rats in each group. Twelve weeks later, the erectile response of all rats was detected by cavernous nerve electric stimulation, and corpus cavernosums were harvested to evaluate the levels of cavernous oxidative stress (OS), apoptosis, fibrosis, and involved pathways. Moreover, cavernous smooth muscle cells (CSMC) and endothelial cells (EC) were primarily isolated to build a coculture system for a series of Conclusions hKLK1 preserves erectile function of DM rats through its antitissue excessive OS, apoptosis, and fibrosis effects, as well as activation of the PI3K/AKT/eNOS/cGMP pathway in the penis. Moreover, hKLK1 promotes relaxation and prevents high glucose-induced injuries of CSMC mediated by EC-CSMC crosstalk.