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目的探讨可溶性鸟苷酸环化酶激活剂Cinaciguat对2型糖尿病大鼠血管并发症的干预作用。方法雄性SD大鼠28只,8只采用普通饲料喂养者为对照组,20只高脂饲料喂养4周后给予小剂量链脲佐菌素腹腔注射制备2型糖尿病大鼠模型,16只大鼠造模成功并随机分为模型组和干预组各8只。继续饲养12周,干预组给予Cinaciguat7μg/(kg·d)腹腔注射,模型组和对照组大鼠给予等量质量分数0.1%DMSO腹腔注射,疗程均为2周。测定各组大鼠血清空腹血糖、糖化血红蛋白、碱性磷酸酶、钙、磷、一氧化氮和一氧化氮合酶水平,并对胸主动脉行组织病理学检查。结果模型组大鼠血清碱性磷酸酶活性[(886.63±527.08)u/L]明显高于干预组[(564.17±475.89)u/L]和对照组[(139.00±32.29)u/L],干预组高于对照组,差异有统计学意义(P<0.01);模型组一氧化氮水平[(43.20±7.49)μmol/L]、一氧化氮合酶活性(12.23±2.32)u/mL]明显低于干预组[(49.18±8.38)μmol/L、(17.43±4.27)u/mL]和对照组[(62.23±10.04)μmol/L、(24.90±5.39)u/mL](P<0.05),干预组低于对照组(P<0.05);干预组和模型组空腹血糖[(24.89±4.79)、(24.60±4.42)mmol/L]及糖化血红蛋白[(11.38±0.61)%、(12.13±0.78)%]水平明显高于对照组[(5.02±0.65)mmol/L、(4.60±0.51)%](P<0.01),模型组与干预组比较差异无统计学意义(P>0.05);对照组、模型组与干预组大鼠血清钙[(1.75±0.17)、(1.89±0.50)、(1.97±0.52)mmol/L]和磷[(2.48±0.12)、(2.85±0.19)、(2.62±0.09)mmol/L]水平比较差异均无统计学意义(P>0.05);组织病理检查结果显示对照组大鼠胸主动脉内膜连续、光滑,中膜平滑肌细胞走行清晰、无增生;模型组大鼠胸主动脉血管壁增厚,中膜平滑肌细胞增生且排列不规则;干预组大鼠胸主动脉壁较为完整、连续,中膜平滑肌细胞稍有增生,排列较规则,走行无明显异常。结论 Cinaciguat能有效改善2型糖尿病大鼠的抗氧化能力,为2型糖尿病血管并发症干预治疗提供了新思路和依据。
Objective To investigate the effects of soluble guanylate cyclase activator Cinaciguat on vascular complications in type 2 diabetic rats. Methods Twenty-eight male Sprague-Dawley rats were fed with normal diet, and 20 rats were fed with high-fat diet for 4 weeks. Small-dose streptozotocin (STZ) was given intraperitoneally to induce type 2 diabetic rats. Sixteen rats The model was successfully established and randomly divided into model group and intervention group, each with 8 rats. The rats in the model group and the control group were intraperitoneally injected with 0.1% DMSO at the same mass for 2 weeks. The rats in the intervention group were intraperitoneally injected with Cinaciguat (7μg / (kg · d)) for 12 weeks. Serum fasting blood glucose, glycosylated hemoglobin, alkaline phosphatase, calcium, phosphorus, nitric oxide and nitric oxide synthase were measured in all groups. Histopathological examination of the thoracic aorta was performed. Results The serum alkaline phosphatase activity in the model group was significantly higher than that in the intervention group [(886.63 ± 527.08) u / L [(564.17 ± 475.89) u / L] and the control group [(139.00 ± 32.29) (43.20 ± 7.49) μmol / L] and nitric oxide synthase activity (12.23 ± 2.32) u / mL in the model group were significantly higher than those in the control group (P <0.01) (49.18 ± 8.38) μmol / L and (17.43 ± 4.27) u / mL in the intervention group and (62.23 ± 10.04) μmol / L and (24.90 ± 5.39) u / mL in the control group, respectively ) In the intervention group and the model group were lower than those in the control group (P <0.05); fasting blood glucose [(24.89 ± 4.79), (24.60 ± 4.42) mmol / L] and HbA1c (11.38 ± 0.61)%, (P <0.01). There was no significant difference between the model group and the intervention group (P> 0.05), but there was no significant difference between the model group and the intervention group (P 0. 05) ; The levels of serum calcium [(1.75 ± 0.17), (1.89 ± 0.50), (1.97 ± 0.52) mmol / L] and phosphorus [(2.48 ± 0.12), (2.85 ± 0.19) (2.62 ± 0.09) mmol / L], there was no significant difference between the two groups (P> 0.05). The results of histopathology showed that the thoracic aorta in the control group had a continuous, smooth, Smooth muscle cells walked clear, no proliferation; thoracic aortic wall thickening of the model group, smooth muscle cell proliferation and irregular arrangement; the thoracic aortic wall in the intervention group is more complete, continuous, medium smooth muscle cells slightly Hyperplasia, arranged more rules, walking no obvious abnormalities. Conclusion Cinaciguat can effectively improve the antioxidant capacity of type 2 diabetic rats and provide new ideas and basis for the interventional treatment of type 2 diabetic vascular complications.