L-精氨酸对糖尿病大鼠睾丸损伤的保护作用

Protective effect of L-arginine on diabetic testicular damage in rats

目的研究L-精氨酸(L-Arg)对糖尿病大鼠睾丸损伤的保护作用及其机制。方法电镜下观察L-Arg对STZ诱导的糖尿病大鼠睾丸的形态学改变,并测定睾丸NO、环磷酸鸟苷(cGMP)、内皮素-1(ET-1)、降钙素基因相关肽(CGRP)、丙二醛(MDA)含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、SOD、Ca^(2+)-ATPase、Na^+-K^+-ATPase活性,RT-PCR检测睾丸内皮型一氧化氮合酶(eNOS)、iNOs、醛糖还原酶(AR)、CGRP及ET-1 mRNA表达。结果糖尿病组大鼠睾丸电镜下主要见到支持细胞胞质内出现较多空泡,并有大量脂滴沉积,与生精细胞接触处出现空泡;NO、cGMP、CGRP含量及NOS、SOD、Ca^(2+)-ATPase、Na^+-K^+-ATPase活性、CGRP、eNOS mRNA表达均明显低于正常对照组(NC组)(P<0.05或P<0.01),而ET-1、MDA含量及AR、ET-1 mRNA表达明显高于NC组(P<0.01)。经L-Arg治疗后,上述改变逆转,与模型组比较,差异有统计学意义(P<0.05或P<0.01),电镜下睾丸组织的形态结构接近于NC组。结论 L-Arg对糖尿病所致的睾丸损伤有一定的保护作用,其机制可能与改善睾丸血供及减轻氧化应激损伤有关。

Objective To investigate the mechanisms of the protective effect of L-arginine（L-Arg） on diabetic testicular damage in rats. Methods Morphology of testis of streptozotocin-induced diabetic rats treated with L-Arg was observed under transmission electron microscope（TEM）. The content of nitric oxide（NO）, malondialdehyde（MDA） and the activity of nitric oxide synthase（NOS）, inducible nitric oxide synthase （iNOS）, superoxide dismutase （SOD）, Ca^2＋-ATPase, Na^＋-K^＋-ATPase in testes homogenate were determined bioehemically, and the levels of cyclic guanosine monophosphate（cGMP）, endothelin-1 （ET-1） and calcitonin gene-related peptide （CGRP） were also detected by radioimmunoassay. In addition, the mRNA expression of NOS, iNOS, AR, CGRP and ET-1 in testis tissue were determined by reverse RT-PCR. Results Obvious vacuoles formation and lots of lipid deposition in the cytoplasm of sertoli cell, and obvious vacuoles at adjoiner between sertoli cells and spermatogenic cells were observed under TEM in diabetes mellitus group. The content of NO, cGMP and CGRP and the activity of NOS, SOD, Ca^2＋-ATPase, Na^＋-K^＋-ATPase as well as CGRP, eNOS mRNA expression were decreased significantly（P〈0.05 or P〈0.01 respectively） but the content of ET-1, MDA and the mRNA expression of AR and ET-1 were increased obviously（P〈 0. 01 respectively） in diabetes mellitus group as compared to those of normal control group. But in L-Arg treated group, the above changes were reversed, there were significant difference compared with those of the diabetes mellitus group （P 〈 0.05 or P 〈 0.01 respectively）. There were plenty of mitoehondria, little lipid deposition and more lysosomes in the cytoplasm of sertoli cell, and plain hierarchical tight-junction between sertoli cells and spermatogenic cells in L-Arg treated groups. Conclusions L-Arg exerts a protective effect on testis in diabetic rats. Regulating the dynamic balance among NO, ET-1 and CGRP in testis, improving its level of blood supply and lessening its oxidative stress damage may be involved in this process.