替米沙坦对1型糖尿病大鼠睾丸组织烟酰胺腺嘌呤二核苷酸氧化酶亚单位p22phox和核因子E2相关因子2表达的影响

Effect of telmisartan on the expression of nicotinamide adenine dinucleotide oxidase subunit p22 phagocyteoxidase and nuclear factor erythroid 2-related factor in the testes of type 1 diabetic rats

目的观察替米沙坦对1型糖尿病大鼠睾丸组织烟酰胺腺嘌呤二核苷酸（NADPH）氧化酶亚单位p22phox和核因子E2相关因子2（NRF．2）表达的影响，探讨替米沙坦对1型糖尿病大鼠睾丸组织的保护作用及机制。方法雄性SD大鼠按随机数字表法分为正常对照组（NC组，n=8）、糖尿病组（DM组，n=8）和替米沙坦治疗组（DT组，n=8）。用链脲佐菌素（STZ）制备1型糖尿病大鼠模型。DT组给予替米沙坦10mg·kg-1·d-1灌胃。替米沙坦治疗8周后留取血标本，用于血生化指标、胰岛素及睾酮水平检测，测定睾丸NADPH氧化酶亚单位p22phox和p47phoxmRNA、NRF-2、超氧化物歧化酶（SOD）、醌氧化还原酶（NQ01）、血红素加氧酶1（HO-1）的表达水平。组间比较采用单因素方差分析，两两比较采用LSD-t检验。结果与Nc组比较，DM组大鼠血糖、睾丸p22phoxmRNA和蛋白表达水平显著升高（分别为27．38±0．82比5．11±0．23，0．95±0．06比0．78±0．12，1．02±0．09比0．59±0．19，t=87．434、3．020、4．610；均P〈0．05）。血胰岛素、血清和睾丸睾酮、睾丸重量、精子数量及活动率、睾丸SOD活性和mRNA表达水平、睾丸NRF-2、NQ01和HO-1mRNA和蛋白表达水平均显著降低（t=2．180—29．396，均P〈0．05）。替米沙坦治疗8周后，DT组大鼠血糖、睾丸p22phoxmRNA和蛋白表达水平均显著低于DM组（t=20．940、4．580、2．860；均P〈O．05）。精子数量及活动率、睾丸SOD活性和mRNA表达水平、睾丸NRF-2和HO-1mRNA和蛋白表达水平、睾丸NQ01蛋白表达水平均显著高于DM组（t=2．00—6．47，均P〈0．05）。结论替米沙坦可对1型糖尿病大鼠睾丸产生保护作用。

Objective To observe the effect of telmisartan on the expression of nicotinamide adenine dinucleotide （NADPH）oxidase subunit p22phox and nuclear factor erythroid 2-related factor（NRF-2） in the testes of type 1 diabetic rats. To investigate the protective effect and mechanism of telmisartan on testicular tissue of type 1 diabetic rats. Methods Male SD rats were randomly divided into normal control （group NC,n=8）,diabetes（group DM, n=8） and diabetes treated with telmisartan（DT,n=8）. Diabetes was induced by a single intraperitoneal injection of streptozotocin. The rats in group DT were given telmisartan in dose of 10 mg/kg once a day by garage. After telmisartan treatment for 8 weeks, blood samples were collected to detect the levels of biochemical index,insulin and testosterone. The expression of testicular NADPH oxidase subunit p22phox and p47phox, NRF-2, superoxide dismutase（SOD）, quinine oxidoreductase I（NQO 1） and heme oxygenase 1（HO-1） were assayed. One-way analysis of variance was used among multiple groups and t analysis was applied for comparison between two groups. Results The levels of blood glucose, mRNA and protein expression of testicular p22phox were significantly increased in group DM than those in group NC （27.38±0.82 vs 5.11±0.23,0.95＋0.06 vs 0.78±0.12, 1.02±0.09 vs 0.59＋0.19, t= 87.434,3.020, 4.610, all P〈0.05）.The levels of serum insulin, serum and testicular testosterone, testieular weight, sperm number and motility, the aetivity and mRNA expression of testieular SOD, and the mRNA and protein expression of testicular NRF-2, NQO1 and HO-1 were signifieantly decreased in group DM than those in group NC （t=2.180-29.396, all P〈0.05 ）. After telmisartan treatment for 8 weeks, the levels of blood glucose, the mRNA and protein expression of testicular p22phox were significantly decreased in group DT than those in group DM （t=20.940, 4.580, 2.860, all P〈0.05）. The levels of sperm number and motility, the activity and mRNA expression of testicular SOD,the mRNA and protein expression of testieular NRF-2, NQO 1 and HO-1 were significantly increased in group DT than those in group DM （t=2.00-6.47, all P〈0.05）. There were no significant differences in serum insulin,serum and testicular testosterone, the expression of testieular NQO1 between group DM and group DT （all P〉0.05）. There was no significant difference in the expression of testicular p47phox among three groups （all P〉0.05）. Conclusions Telmisartan may play a proteetive role on testieular tissues in type 1 diabetic rats.