探讨地龙蛋白对糖尿病性勃起功能障碍（DMED）大鼠阴茎海绵体平滑肌细胞（CCSMC）表型转化及 其勃起功能的影响。方法将60 只勃起功能正常的雄性SD 大鼠随机分为空白组、模型组、西地拉非组 （5 mg·kg-1）及地龙蛋白低、中、高剂量组（45、90、180 mg·kg-1），每组10 只。采用腹腔注射链脲佐菌素 （STZ，50 mg·kg-1）结合高脂饲料喂养建立糖尿病大鼠模型；8 周后，颈部注射阿朴吗啡（APO，100 μg·kg-1）， 制备DMED 大鼠模型。造模成功后，按剂量灌胃给药，每日1 次，连续4 周。测定各组大鼠造模前、造模 第3 天、给药4 周后的血糖水平及体质量。采用多导生理记录仪测定大鼠阴茎海绵体内压（ICP）、颈动脉内压 （MAP），计算ICP/MAP 比值；免疫组织化学法检测阴茎海绵体中收缩型标志物α-平滑肌肌动蛋白（α-SMA）、 平滑肌肌球蛋白重链（SMMHC）和合成型标志物Ⅰ型胶原蛋白（CollagenⅠ）、骨桥蛋白（OPN）表达情况； RT-PCR 法检测阴茎海绵体中α-SMA、SMMHC、CollagenⅠmRNA 表达水平；Western Blot 法检测阴茎海绵体 中α-SMA、肌间线蛋白（Desmin）、CollagenⅠ、OPN 蛋白表达水平。结果与空白组比较，模型组大鼠在造模 第3 天和给药4 周后的血糖值均显著升高（P＜0.01），给药4 周后的体质量显著降低（P＜0.01）；ICP 及ICP/ MAP 比值显著降低（P＜0.01）；阴茎海绵体中α-SMA、SMMHC、Desmin 蛋白表达水平显著降低（P＜0.01）， Collagen Ⅰ、OPN 蛋白表达水平显著升高（P＜0.01）；阴茎海绵体中α-SMA、SMMHC mRNA 表达水平显著降 低（P＜0.01），Collagen Ⅰ mRNA 表达水平显著升高（P＜0.01）。与模型组比较，给药组大鼠的血糖值及体质量 均无明显变化（P＞0.05）；ICP 及ICP/MAP 比值均显著升高（P＜0.01）；阴茎海绵体中α-SMA、SMMHC、 Desmin 蛋白表达水平显著升高（P＜0.01），Collagen Ⅰ、OPN 蛋白表达水平显著降低（P＜0.01）；阴茎海绵体中 α-SMA、SMMHC mRNA 表达水平显著升高（P＜0.01），Collagen Ⅰ mRNA 表达水平显著降低（P＜0.01）。 结论地龙蛋白能够改善DMED 大鼠勃起功能，其机制可能与通过抑制CCSMC 由“收缩型”向“合成型（增 殖型）”转化有关。

To investigate the effect of Lumbricus protein on the phenotypic transformation of corporal cavernosum smooth muscle cells （CCSMC） and erectile function in diabetic erectile dysfunction （DMED） rats.Methods Sixty male SD rats with normal erectile function were randomly divided into a blank group，a model group， a Sildelafil group （5 mg·kg-1），and a Lumbricus protein low-，medium-，and high-dose group （45，90，and 180 mg·kg-1）， with 10 rats in each group. The diabetic rat model was established by intraperitoneal injection of Streptozotocin （STZ，50 mg·kg-1） combined with high-fat feed feeding；after 8 weeks，the DMED rat model was prepared by neck injection of Apomorphine （APO， 100 μg · kg-1） . After successful modeling， the rats were administered with a dose of Apomorphine by gavage once a day for 4 weeks. The blood glucose levels and body mass of rats in each group were measured before modeling， on the third day of modeling， and after 4 weeks of drug administration. The intracavernous pressure （ICP） and carotid artery pressure （MAP） were measured by multichannel physiological recorder， and the ICP/MAP ratio was calculated. The expressions of contractile markers α- smooth muscle actin （α-SMA），smooth muscle myosin heavy chain （SMMHC） and synthetic markers Collagen I and osteopontin （OPN） in corpus cavernosum were detected by immunohistochemistry. The mRNA expression levels of α-SMA，SMMHC and Collagen I in corpus cavernosum were detected by RT-PCR. The protein expression levels of α-SMA，Desmin，Collagen I and OPN in corpus cavernosum were detected by Western Blot. Results Compared with the blank group，the blood glucose levels of the rats in the model group were significantly increased on the third day of modeling and after 4 weeks of administration （P＜0.01），and the body mass was significantly decreased after 4 weeks of administration （P＜0.01） . ICP and ICP / MAP ratio were significantly decreased （P＜0.01） . The protein expression levels of α-SMA，SMMHC and Desmin in penile corpus cavernosum were significantly decreased （P＜0.01），and the protein expression levels of Collagen I and OPN were significantly increased （P＜0.01） . The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly decreased （P＜0.01），and the mRNA expression level of Collagen I was significantly increased （P＜0.01） . Compared with the model group， there was no significant change in blood glucose and body mass of rats in the administration group （P＞0.05） . ICP and ICP/MAP ratio were significantly increased （P＜0.01） . The expression levels of α-SMA，SMMHC and Desmin in corpus cavernosum were significantly increased （P＜0.01）， while the expression levels of Collagen I and OPN were significantly decreased（P＜0.01） . The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly increased （P＜0.01）， and the mRNA expression level of Collagen I was significantly decreased （P＜0.01） . Conclusion Lumbricus protein can improve the erectile function of DMED rats， and its mechanism may be related to the inhibition of CCSMC from 'contractile' to 'synthetic（proliferative）' transformation

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甘肃省中医药管理局基金项目（GZKP-2021-18）；甘肃省中医药防治慢性病重点实验室开放基金项目（GSMBKY2015-13）；甘肃中医药 大学附属医院院内课题（gzfy-2019-07）。