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目的观察PRMT1-ADMA-DDAH1代谢轴在糖尿病大鼠胰腺中的表达,及普罗布考对其表达和胰岛功能的影响。方法将30只雄性SD大鼠分为正常对照组(C组,n=10)、糖尿病组(D组,n=10)、糖尿病普罗布考干预组(P组,n=10)。用高脂高糖喂养联合腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型,干预组以普罗布考500mg/(kg.d)灌胃。药物干预8周后收集3组大鼠胰腺组织,ELISA法检测ADMA的浓度,用RT-PCR检测PRMT1、DDAH1 mRNA的表达,Western blot观察PRMT1蛋白的表达,免疫组化法观察胰岛素和PRMT1的表达;同时采集3组大鼠的血液标本,测定胰岛功能指标空腹血糖(FBG)、空腹血胰岛素(FINS)及氧化应激指标丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的水平。结果 C、D、P组大鼠胰腺组织中ADMA的浓度分别为(464.50±53.83)、(1255.34±188.00)、(891.72±52.10)μmol/L,D组、P组明显高于C组(P<0.01),P组显著低于D组(P<0.01);D组和P组大鼠的PRMT1 mRNA表达明显高于C组(P<0.01)、但P组明显低于D组(P<0.01),与C组相比,D、P组大鼠DDAH1的mRNA表达明显降低(P<0.01),与D组相比,P组中DDAH1的mRNA表达明显升高(P<0.01);Western blot和免疫组化的结果显示,D组与P组的PRMT1蛋白表达明显高于C组(P<0.01);而P组又明显低于D组(P<0.01)。结论糖尿病状态下,大鼠胰腺组织的PRMT1-ADMA-DDAH1代谢轴中PRMT1的表达升高,DDAH1的表达降低,导致ADMA的浓度升高,加剧氧化应激,使胰岛功能下降。而普罗布考通过其抗氧化作用,可以在一定程度上调节糖尿病状态下胰腺的PRMT1-ADMA-DDAH1代谢轴的表达,从而抑制氧化应激,改善胰岛功能。
Objective To observe the expression of PRMT1-ADMA-DDAH1 axis in the pancreas of diabetic rats and the effect of probucol on its function and islet function. Methods Thirty male Sprague-Dawley rats were divided into normal control group (n = 10 in group C), diabetic group (n = 10 in group D), and probiotics in diabetic group (n = 10). Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ). The rats in the intervention group were fed with probucol 500 mg / (kg.d) orally. After 8 weeks of intervention, the pancreas tissues of three groups were collected. The concentration of ADMA was detected by ELISA. The expression of PRMT1 and DDAH1 mRNA was detected by RT-PCR. The expression of PRMT1 protein was detected by Western blot. The expression of insulin and PRMT1 was observed by immunohistochemistry Blood samples of three groups were collected at the same time to measure fasting blood glucose (FBG), fasting insulin (FINS) and oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD) Hydrogenase (CAT) levels. Results The concentrations of ADMA in C, D and P groups were (464.50 ± 53.83), (1255.34 ± 188.00) and (891.72 ± 52.10) μmol / L, respectively, and those in group D and P were significantly higher than those in group C (P <0.01). The expression of PRMT1 mRNA in group D and group P was significantly higher than that in group C (P <0.01), but the level in group P was significantly lower than that in group D (P < 0.01). Compared with group C, DDAH1 mRNA expression in group D and group P decreased significantly (P <0.01). Compared with group D, DDAH1 mRNA expression in group P increased significantly (P <0.01); Western The results of blot and immunohistochemistry showed that the expression of PRMT1 protein in group D and group P was significantly higher than that in group C (P <0.01), while the level in group P was significantly lower than that in group D (P <0.01). Conclusions The expression of PRMT1 and the expression of DDAH1 in the PRMT1-ADMA-DDAH1 metabolic axis of rat pancreatic tissue are increased under the condition of diabetes mellitus, resulting in the increase of ADMA concentration and exacerbation of oxidative stress, leading to the decrease of pancreatic islet function. Probucol, through its anti-oxidant effect, regulates the expression of the PRMT1-ADMA-DDAH1 metabolic axis of the pancreas in diabetic states to a certain extent, thereby inhibiting oxidative stress and improving pancreatic islet function.