复方血栓通胶囊对糖尿病肾病大鼠肾脏保护作用的机制初探

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

目的探讨复方血栓通胶囊对糖尿病肾病大鼠肾脏的保护作用。方法8周龄雄性SD大鼠用链脲佐菌素单次腹腔注射建立糖尿病肾病模型后，分为4组：糖尿病肾病组、厄贝沙坦组（安博维片20mg·kg^-1·d^-1）、血栓通低剂量组（血栓通胶囊900mg·kg^-1·d^-1）、血栓通高剂量组（血栓通胶囊1800mg·kg^-1·d^-1）（每组7只）。均采用灌胃给药。另选取7只健康同龄大鼠作为正常组。干预12周后，测定尿白蛋白；行苏木精-伊红染色、马松染色观察肾脏组织病理变化；检测血一氧化氮（NO），脂质过氧化物的产物丙二醛（MDA）含量和血、尿超氧化物歧化酶（SOD）活性；蛋白免疫印迹法测定肾皮质基质金属蛋白酶2（MMP-2）的表达。结果糖尿病肾病组大鼠的尿白蛋白高于正常组[（981±111）μg/24h比（32±3）μg／24h]，3种不同干预组尿白蛋白均有降低[（240±20）μg／24h、（577±57）μg／24h、（647±55）μg／24h]；肾脏病理检查提示厄贝沙坦组、血栓通组可缓解细胞外基质沉积，改善肾小球硬化；糖尿病肾病组MMP-2高表达，但不同干预组对MMP-2的表达均无影响；与糖尿病肾病组相比，血栓通低剂量组高剂量组的血NO[（104．9±11．0）μmol／L比（41．9±9．6）μmol／L、（14．7±1．9）μmol／L，P〈0．05]和血MDA含量均低[（19．6±1．6）nmol／L比（6．6±0．9）nmoL／L、（4．5±1．2）nmol／L，P〈0．05]，血和尿SOD活性[血（222±20）×10^3 U／L比（231±18）×10^3U／L、（237±24）×10^3 U／L，P〈0．05；尿（11．8±1．1）×10^3 U／L比（23．3±2．0）×10^3U／L、（25．7±1．8）×10^3U／L，P〈0．05]增加。结论复方血栓通胶囊减少糖尿病肾病大鼠尿白蛋白，可能与抗氧化应激有关，而与改善细胞外基质代谢无关。

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 hyperglycerimia （3 days later, fasting bood 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 highdosage XST （1800 mg±kg^-l± d^-l）. 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 superoxidedismutase （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 hypermicroalbuminuria. 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 highdosage 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） μmo]/L, P 〈 0. 05 ） and MDA （ （ 19. 6 ±1.6 ） nmol/L vs （6. 6±0. 9） nmoL/L and （4. 5± 1.2 ） nmoL/L, P 〈 0. 05 ）, increased blood and urine activities of SOD （ blood ： （ 222±20） ×10^3vs （231±18） ×l0^3 and （237 ±24） ×l0^3 U/L,P 〈0.05）, urine： （11.8±1.1）×10^3 vs（23.3±2.0） x 103 and （ 25.7 ±1.8 ） x 10^3 U/L）. Conclusion Compound Xueshuantong Capsule may decrease proteinuria through its suppression of oxidative stress and not its improvement of ECM metabolism.