补阳还五汤对糖尿病性勃起功能障碍大鼠阴茎海绵体纤维化及RhoA、ROCK2蛋白表达的影响  

Effects of Buyang Huanwu Decoction on Cavernosal Fibrosis and the Protein Expression of RhoA and ROCK2 in the Penis of Diabetic Mellitus-Related Erectile Dysfunction Rats

作　　者：叶妙勇 赵凡 王军卫 石兵 王伟[3] 马健雄[4,5] YE Miao-yong;ZHAO Fan;WANG Jun-wei;SHI Bing;WANG Wei;MA Jian-xiong(Department of Urology,The Affiliated Wenling Hospital of Wenzhou Medical University,Zhejiang 317500;Department of Urology,Affiliated Hospital of Nantong University,Jiangsu 226000;Department of Urology,Nantong Hospital of Traditional Chinese Medicine,Jiangsu 226000;Department of Andrology,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700;The Second Clinical Medical College,Zhejiang Chinese Medical University,Hangzhou 310000)

机构地区：[1]温州医科大学附属温岭医院泌尿外科,浙江317500 [2]南通大学附属医院泌尿外科,江苏226000 [3]南通市中医院泌尿外科,江苏226000 [4]北京中医药大学东直门医院男科,北京100700 [5]浙江中医药大学第二临床医学院,杭州310000

出　　处：《中国中西医结合杂志》2022年第11期1369-1375,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.82004360,No.81804092);浙江省自然科学基金资助项目(No.GF20H270004);温岭市科技计划项目(No.2018C310012,No.2021S00219);南通市基础科学研究计划面上项目(No.JCZ2022044);南通大学附属医院博士科研启动基金项目(No.Tdb2006);浙江中医药大学研究生科研基金(No.2021YKJ04);浙江省大学生新苗人才计划(No.2022R410B056)。

摘　　要：目的观察补阳还五汤(BHD)对糖尿病性勃起功能障碍(DMED)的作用,并探讨其作用机制。方法经腹腔注射链脲佐菌素制备糖尿病DMED大鼠模型,通过阿扑吗啡实验筛选DMED大鼠。将36只DMED大鼠分为模型组、低、中、高剂量BHD组,每组9只。另取9只同月龄SD大鼠作为正常组。低、中、高剂量BHD组分别给予12.8、25.6、51.2 g/(kg·d)BHD灌胃,正常组和模型组给予等量生理盐水灌胃。测量阴茎海绵体内压(ICP)及ICP曲线下面积(AUC)/平均动脉压(MAP)观察勃起功能;Masson染色检测海绵体纤维化程度;免疫组化技术检测阴茎海绵体Ras同源基因家族成员A(RhoA)、Rho相关卷曲螺旋蛋白激酶2(ROCK2)蛋白表达;Western Blot检测阴茎海绵体α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)、RhoA、ROCK2蛋白表达。结果与正常组比较,模型组ICP峰值、AUC/MAP、阴茎海绵体平滑肌面积、平滑肌/胶原纤维、α-SMA蛋白表达降低(P<0.05),TGF-β1、RhoA、ROCK2蛋白表达升高(P<0.05)。与模型组比较,中、高剂量BHD干预后ICP峰值、AUC/MAP、阴茎海绵体平滑肌面积、平滑肌/胶原纤维、α-SMA蛋白表达升高(P<0.05),TGF-β1、RhoA、ROCK2蛋白表达降低(P<0.05)。结论BHD可有效改善DMED大鼠勃起功能,其作用机制可能与抑制阴茎海绵体纤维化、维持其平滑肌含量以及抑制RhoA/ROCK2信号蛋白表达有关。Objective To observe the therapeutic effect of Buyang Huanwu Decoction(BHD)on diabetic erectile dysfunction(DMED)and explore its mechanism.Methods The diabetes rat model was prepared via intraperitoneal injection of streptozotocin,DMED rats were selected by apomorphine test.Totally 36 DMED rats were divided into model group,low,medium and high dose BHD group,9 rats in each group,another 9 same age SD rats were recruited as normal group.The low,medium and high doses BHD group were given 12.8,25.6 and 51.2 g/(kg·d)of BHD by gavage respectively,while the normal and model groups were given equal amounts of saline by gavage.The intracavernosal pressure(ICP)and area under the ICP curve(AUC)/mean arterial pressure(MAP)were measured to observe the erectile function.Masson staining was performed to detect the degree of cavernous fibrosis.Ras homolog gene family member A(RhoA)and Rho associated coiled-coil containing protein kinase 2(ROCK2)protein expression were detected by immunohistochemistry.α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1),RhoA and ROCK2 protein expression were detected by Western Blot.Results Compared with normal group,ICP,AUC/MAP,penile cavernous smooth muscle area,smooth muscle/collagen fibers,andα-SMA protein expression decreased(P<0.05),TGF-β1,RhoA,and ROCK2 protein expression increased in model group(P<0.05).Compared with model group,ICP,AUC/MAP,penile cavernous smooth muscle area,smooth muscle/collagen fibers,andα-SMA protein expression increased(P<0.05),TGF-β1,RhoA,and ROCK2protein expression decreased(P<0.05)in medium and high-dose BHD group.Conclusion BHD can effectively improve the erectile function of DMED rats,and its mechanism may be related to inhibiting penile cavernous fibrosis,maintaining its smooth muscle content,and regulating the expression of RhoA/ROCK2 signaling protein.

关 键 词：补阳还五汤 糖尿病性勃起功能障碍 阴茎海绵体纤维化 Ras同源基因家族成员A Rho相关卷曲螺旋蛋白激酶2 

分 类 号：R285.5[医药卫生—中药学]