丹参和三七对实验性糖尿病小鼠心肾组织纤维化病变的影响及其作用机制研究

目的:探讨丹参和三七对实验性糖尿病小鼠心肾组织纤维化病变的影响及其可能的作用机制。方法:采用一次性尾静脉注射四氧嘧啶造成小鼠糖尿病模型,饲养6周后随机分为7组,其中组1为糖尿病对照组(DM组),其余6组加用左旋N硝基精氨酸制备糖尿病小鼠心、肾组织纤维化模型。然后将组2设为糖尿病-组织纤维化模型对照组(DML组),3～7组则分别给予格列奇特(组3)或格列奇特加高、低剂量的丹参(组4、组5)和三七(组6)及依那普利(组7)。计算用药前后各组的心、肾脏器系数,检测血浆和心肾组织中一氧化氮、羟脯氨酸及丙二醛的含量和诱导型一氧化氮合酶、内皮型一氧化氮合酶的活性。结果:与DML模型组比较,丹参高剂量组(组4)血浆、心、肾组织中的一氧化氮含量显著增加,其提高率分别为298.4%、143.1%和189.5%;内皮型一氧化氮合酶的活性显著提高,其提高率分别为64.3%、67.6%和113.0%;心、肾组织中丙二醛、羟脯氨酸的含量也明显降低,丙二醛的降低率分别为45.5%和40.3%,羟脯氨酸的降低率分别为19.3%和17.6%。结论:在给予基础降糖药的基础上,合并给予丹参能对抗实验性糖尿病小鼠心肾组织纤维化,而合并给予三七的药效相对较弱。

The Effects and Mechanisms of Salvia Miltiorrhizae and Radix Notoginseng on Fibrosis of Organs in Diabetic Mice

Objective: To study the mechanisms and effects of Salvia miltiorrhizae and Radix notoginseng on anti-fibrosis in alloxan -L-NNA-induced diabetic fibrosis model mice. Methods: 140 model mice with diabetes were established by alloxan (iv). Followed by six weeks, these mice were divided into seven groups: group 1 was control group (DM group) and the other groups were administered by L-NNA for preparing fibrotic models. Group 2 was DML control group and the other groups were treated with gliclazide tablets (group 3)and high or low dosage of Salvia miltiorrhizae (group 4 or group 5)or Radix notoginseng (group 6) or enalapril mateate tablets(group 7), respectively.The changes of heart and kidney index before and after being treated with these medicines were recorded. The contents of nitric oxide, hydroxyproline, malonaldehyde and the activity of endothelial nitric oxide synthetase and inducible nitric oxide synthetase in plasma, heart and kidney were assayed. Results: In comparison with DML control group,the contents of nitric oxide in plasma, heart and kidney in the group 4 (high-dosage of Salvia miltiorrhizae group) were improved remarkably and the ratio of change were 298.4%, 143.1% and 189.5%, respectively. In group 4, the activity of endothelial nitric oxide synthetase in plasma, heart and kidney were also increased and the ratio of change were 64.3%, 67.6% and 113.0%, respectively. Simultaneously, the contents of malonaldehyde and hydroxyproline in group 4 were decreased by 45.5% and 19.3% in heart, and 40.3% and 17.6% in kidney. Conclusion: The anti-fibrosis activity of Salvia miltiorrhizae is stronger than that of Radix notoginseng when combined with gliclazide tablets in alloxan-L-NNA-induced diabetic fibrosis model mice.