复方血栓通胶囊对糖尿病肾病大鼠的保护作用及机制

[Protection effect and mechanism of Compound Xueshuantong Capsule on diabetic nephropathy rats].

作者信息

Yan Jin-hua, Xia Xuan, Zhu Yan-hua, Xu Fen, Zhang Lei, Zhao Yi, Liang Hua, Weng Jian-ping

机构信息

Department of Endocrinology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2012 Aug 14;92(30):2099-103.

PMID:23158271

Abstract

OBJECTIVE

To explore the renoprotective effect of Compound Xueshuantong Capsule (XST) on diabetic rat model with nephropathy.

METHODS

Twenty-eight male Sprague Dawley diabetic rats were induced to hyperglycaemia (3 days later, fasting blood glucose > 16.7 mmol/L) by peritoneal injection with streptozotocin (STZ, 50 mg/kg). And they were divided into four groups: diabetic nephropathy (vehicle treatment), irbesartan (20 mg×kg(-1)×d(-1)), low-dosage XST (900 mg×kg(-1)×d(-1)) and high-dosage XST (1800 mg×kg(-1)×d(-1)). Seven normal rats were used as control. After a 12-week intervention, urine protein was examined. Pathological morphology was observed by hematoxylin-eosin (HE), Masson and (periodic acid Schiff) PAS stains. Blood nitric oxide (NO), malondialdehyde (MDA) and blood superoxide dismutase (SOD) and urine SOD were detected. And the expression of (matrix metalloproteinase-2) MMP-2 was detected by Western blot in each group.

RESULTS

The model rats presented with hyperglycemia, polydipsia, hyperphagia, polyuria and hyper microalbuminuria. The intervention groups showed decreased microalbuminuria and there was no effect on blood glucose or body weight. Glomerular sclerosis and extracellular matrix (ECM) increased in model group and improved in irbesartan and XST groups as judged by HE, Masson and PAS stains. Three intervention groups had no effect on the elevated expression of MMP-2 in diabetic rats. Compared with the model group, the irbesartan, low-dosage and high-dosage XST groups had significantly decreased blood levels of NO ((104.9 ± 11.0) µmol/L vs (41.9 ± 9.6) µmol/L and (14.7 ± 1.9) µmol/L, P < 0.05) and MDA ((19.6 ± 1.6) nmol/L vs (6.6 ± 0.9) mol/L and (4.5 ± 1.2) nmol/L, P < 0.05), increased blood and urine activities of SOD (blood: (222 ± 20)×10(3) vs (231 ± 18)×10(3) and (237 ± 24)×10(3) U/L,P < 0.05), urine: (11.8 ± 1.1)×10(3) vs (23.3 ± 2.0)×10(3) and (25.7 ± 1.8)×10(3) U/L).

CONCLUSION

Compound Xueshuantong Capsule may decrease proteinuria through its suppression of oxidative stress and not its improvement of ECM metabolism.

摘要

目的

探讨复方血栓通胶囊（XST）对糖尿病肾病大鼠模型的肾脏保护作用。

方法

28只雄性Sprague Dawley糖尿病大鼠通过腹腔注射链脲佐菌素（STZ，50 mg/kg）诱导高血糖（3天后，空腹血糖>16.7 mmol/L）。将它们分为四组：糖尿病肾病组（赋形剂治疗）、厄贝沙坦组（20 mg×kg⁻¹×d⁻¹）、低剂量XST组（900 mg×kg⁻¹×d⁻¹）和高剂量XST组（1800 mg×kg⁻¹×d⁻¹）。7只正常大鼠作为对照。经过12周干预后，检测尿蛋白。通过苏木精-伊红（HE）、Masson和（过碘酸希夫）PAS染色观察病理形态。检测血中一氧化氮（NO）、丙二醛（MDA）、血超氧化物歧化酶（SOD）和尿SOD。并通过蛋白质印迹法检测各组中（基质金属蛋白酶-2）MMP-2的表达。

结果

模型大鼠出现高血糖、多饮、多食、多尿和高微量白蛋白尿。干预组微量白蛋白尿减少，对血糖或体重无影响。HE、Masson和PAS染色显示，模型组肾小球硬化和细胞外基质（ECM）增加，厄贝沙坦和XST组有所改善。三个干预组对糖尿病大鼠中升高的MMP-2表达无影响。与模型组相比，厄贝沙坦、低剂量和高剂量XST组血中NO水平显著降低（（104.9±11.0）µmol/L对（41.9±9.6）µmol/L和（14.7±1.9）µmol/L，P<0.05）和MDA水平显著降低（（19.6±1.6）nmol/L对（6.6±0.9）mol/L和（4.5±1.2）nmol/L，P<0.05），血和尿中SOD活性增加（血：（222±20）×10³对（231±18）×10³和（237±24）×10³ U/L，P<0.05），尿：（11.8±1.1）×10³对（23.3±2.0）×10³和（25.7±1.8）×10³ U/L）。