乙醇激活ALDH2对2型糖尿病大鼠睾丸损伤的影响

摘要

目的：观察乙醇激活乙醛脱氢酶2(ALDH2)对2型糖尿病大鼠睾丸损伤的影响。方法健康♂SD大鼠高糖高脂饮食联合低剂量链脲佐菌素(STZ)(35 mg·kg-1)制备2型糖尿病大鼠模型。成模后,将大鼠随机分为正常对照组、2型糖尿病组、乙醇+2型糖尿病组(n=6)。乙醇+2型糖尿病组大鼠先给予体积分数0．025乙醇喂养1周后,改用体积分数0．05乙醇继续喂养7周；正常对照组和2型糖尿病组大鼠常规喂养8周。8周后,测定血糖、糖化血红蛋白、血清睾酮、睾丸质量系数等指标,观察睾丸组织结构改变,检测睾丸组织ALDH2 mRNA、转化生长因子β1( TGF-β1) mRNA水平和TGF-β1阳性率的变化。结果与正常对照组比较,2型糖尿病组大鼠血糖、糖化血红蛋白和睾丸质量系数均明显升高,血清睾酮水平明显降低,睾丸组织中部分生精小管萎缩,各级生精细胞减少,排列疏松,睾丸间质细胞减少,睾丸组织ALDH2 mRNA 水平明显减少, TGF-β1 mRNA 水平和TGF-β1阳性率明显升高。给予乙醇干预后,与2型糖尿病组比较,乙醇+2型糖尿病组大鼠血糖、糖化血红蛋白和睾丸质量系数降低,血清睾酮水平升高,病理改变减轻,睾丸组织ALDH2 mRNA水平明显升高、TGF-β1 mRNA水平和TGF-β1阳性率明显降低。结论激活 ALDH2可能通过下调TGF-β1的表达,减轻2型糖尿病对睾丸的损伤。%Aim To observe the effects of activation of aldehyde dehydrogenase 2 ( ALDH2 ) by ethanol on testis injury of type 2 diabetic rats. Methods Type 2 diabetic rats model were established by high-fat diet combined with low-dose streptozotocin ( STZ ) injec-tions. After the success of modeling, the rats were ran-domly divided into 3 groups ( n =6 ): normal control group (NC), type 2 diabetes group (T2DM) and eth-anol+type 2 diabetes group (EtOH+T2DM). Rats of EtOH + T2DM were treated with low-dose ethanol, then rats of NC and T2 DM were given normal diet for 8 weeks. After 8 weeks, the levels of the fasting blood glucose ( FBG ) , glycosylated hemoglobin ( HbA1 c ) and testosterone were tested, and the ratio of testis weight to body weight ( TW/BW ) was calculated. Morphological changes of testis tissue were observed by optical microscope. The levels of ALDH2 mRNA and transforming growth factorβ1 ( TGF-β1 ) mRNA in tes-tis tissue were measured. The expression of TGF-β1 in testis tissue was observed by immunohistochemical stai-ning, then the positive rate of TGF-β1 was calculated. Results Compared with NC, the levels of FBG, HbA1 c and TW/BW increased significantly and the level of testosterone decreased significantly in T2DM. The morphological observation showed that some semi-niferous tubules atrophied, spermatogenic cells de-creased and arrangemented loosely, Leydig cells de-creased in testicular interstitial. The level of ALDH2 mRNA in testis tissue decreased significantly, and the level of TGF-β1 mRNA and the positive rate of TGF-β1 in testis tissue increased significantly. However, compared with T2DM, the levels of FBG, HbA1c and TW/BW decreased, and the level of testosterone in-creased and the damage of testis tissue was attenuated in EtOH+T2DM. The level of ALDH2 mRNA in testis tissue increased significantly, and the level TGF-β1 mRNA and the positive rate of TGF-β1 in testis tissue decreased significantly. Conclusion Activating AL-DH2 can protect testis in type 2 diabetic rats, which may be related to the downregulation of TGF-β1 ex-pression.