J Tradit Chin Med. 2014 Oct;34(5):597-603. doi: 10.1016/s0254-6272(15)30069-8.
To investigate the correlativity between the changes of blood measures related to blood stasis blocking collaterals and gene expression levels of angiotensin-converting enzyme (ACE) and ACE2 of renal cortex in diabetic rats with stasis blocking collaterals syndrome, as well as the effect of stasis removing and collaterals dredging.
Male Sprague-Dawley rats were divided randomly into normal control group (C group), high-carbohydrate-fat control group (H group) and streptozotocin (STZ)-injecting group. The diabeticrats were induced from rats in the STZ-injecting, group by high-carbohydrate-fat diet combined with STZ intraperitoneal injection, with sustained high-carbohydrate-fat diet fed afterwards, and were further divided into model group (M group) and Chinese medicine of stasis removing and collaterals dredging group (Z group). Rats in the Z group were fed with stasis-removing-and-collaterals-dredging herbal granule suspension intragastrically daily for 16 weeks, while drinking water of corresponding volume was administrated to the rats in other groups. At the end of the 16th week after successful establishment of models, the ultrastructures of glomeruli in different groups were detected by a transmission electron microscopy; and blood measures related to blood stasis blocking collaterals, including lipid profile and blood viscosity measures, were tested, as well as the relative gene expressions of ACE and ACE2.
Changes in ultrastructures of glomeruli in the M group were characterized by lack of clarity in structure and occasional thickening of glomerular basement membrane and extensive fusion in foot processes. The correlation analysis showed that there were positive correlations between lipid profile, blood viscosity, and the ACE mRNA expression levels in the M group (P < 0.05), except for cholesterol. And except for triglyceride, the blood measures were in negative correlation with the ACE2 mRNA expression levels in the M group (P < 0.05). Compared with the C and H groups, the lipid profile, plasma viscosity and blood viscosity were significantly higher (P < 0.01). All the above-mentioned measures were significantly improved in the Z group rats (P < 0.05). ACE mRNA expression was significantly higher in the M group than in the C group(P < 0.05). ACE2 mRNA level was significantly lower in the M group than in the C and H groups (P < 0.01); and its level in the Z group was higher than that in the M group (P < 0.01).
Blood measures related to blood stasis blocking collaterals had positive linear correlations with ACE mRNA expression and negative linear correlations with ACE2 mRNA expression in the M group. Chinese recipe of stasis removing and collaterals dredging could play a renal protecting role for diabetic rats by reducing lipid profile and blood viscosity, down-regulating ACE mRNA expression and up-regulating ACE2 mRNA expression.
探讨糖尿病血瘀证大鼠血瘀证相关血液学指标的变化与肾皮质血管紧张素转换酶(ACE)和 ACE2 基因表达水平的相关性,以及化瘀通络中药的作用。
雄性 Sprague-Dawley 大鼠随机分为正常对照组(C 组)、高糖高脂对照组(H 组)和链脲佐菌素(STZ)注射组。STZ 注射组大鼠通过高糖高脂饮食联合腹腔注射 STZ 诱导糖尿病,随后给予持续高糖高脂饮食,并进一步分为模型组(M 组)和化瘀通络中药组(Z 组)。Z 组大鼠每日灌胃化瘀通络中药颗粒混悬液,其他各组给予相应体积的饮用水。模型建立成功后的第 16 周末,采用透射电镜观察各组肾小球超微结构;检测血瘀证相关血液学指标,包括血脂谱和血液黏度指标,以及 ACE 和 ACE2 的相对基因表达。
M 组肾小球超微结构变化表现为结构不清,偶尔出现肾小球基底膜增厚和足突广泛融合。相关性分析显示,M 组血脂谱、血液黏度与 ACE mRNA 表达水平呈正相关(P<0.05),除胆固醇外。除甘油三酯外,M 组血液学指标与 ACE2 mRNA 表达水平呈负相关(P<0.05)。与 C 组和 H 组相比,M 组血脂谱、血浆黏度和血液黏度显著升高(P<0.01)。Z 组大鼠上述各项指标均明显改善(P<0.05)。M 组 ACE mRNA 表达明显高于 C 组(P<0.05)。M 组 ACE2 mRNA 水平明显低于 C 组和 H 组(P<0.01);Z 组高于 M 组(P<0.01)。
M 组血瘀证相关血液学指标与 ACE mRNA 表达呈正线性相关,与 ACE2 mRNA 表达呈负线性相关。化瘀通络中药可通过降低血脂谱和血液黏度,下调 ACE mRNA 表达,上调 ACE2 mRNA 表达,对糖尿病大鼠发挥肾脏保护作用。