单侧输尿管梗阻肾间质纤维化模型大鼠与川芎嗪的干预

Effects of tetramethylpyrazine in rats with unilateral ureteral obstruction renal fibrosis

背景:肾间质纤维化与组织基质金属蛋白酶2和金属蛋白酶组织抑制因子2表达失衡有关。目的:建立单侧输尿管梗阻肾纤维化模型,观察川芎嗪治疗后肾间质病理变化及肾组织组织基质金属蛋白酶2和金属蛋白酶组织抑制因子2的表达变化。方法:24只雌性SD大鼠分为3组,除假手术组外,模型组及川芎嗪组均在无菌条件下行左侧输尿管结扎建立单侧输尿管梗阻模型,川芎嗪组于术前1d开始灌胃给药,40mg/(kg·d),1次/d,连续2周。术后14d处死各组大鼠,留取梗阻侧肾组织行苏木精-伊红染色和Masson染色以观察肾组织病理改变,免疫组化和反转录-聚合酶链反应方法检测肾组织基质金属蛋白酶2、金属蛋白酶组织抑制因子2的表达水平。结果与结论:川芎嗪组可明显减轻肾小管的扩张和萎缩,减轻肾间质纤维组织增生及炎性细胞浸润。与假手术组相比,模型组基质金属蛋白酶2、金属蛋白酶组织抑制因子2蛋白和mRNA基因表达均明显增加(P<0.01);川芎嗪组上述物质表达较模型组明显减少(P<0.01)。提示川芎嗪通过下调基质金属蛋白酶2、金属蛋白酶组织抑制因子2的表达,从而改善单侧输尿管梗阻大鼠的肾间质纤维化。

BACKGROUND： Renal interstitial fibrosis is related to the imbalance between matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2. OBJECTIVE： To establish the unilateral ureteral obstruction renal fibrosis model and to observe the pathological changes of renal interstitial and the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 after treated with tetramethylpyrazine. METHODS： Twenty-four female Sprague Dawley rats were randomly divided into three groups： sham-operation group, model group and tetramethylpyrazine group. The rats in the model group and tetramethylpyrazine group were performed with left ureter ligation to establish the unilateral ureteral obstruction model. Rats in the tetramethylpyrazine group were performed with intragastric administration at t day before surgery, 40 mg/（kg·d） once per day and lasted for 2 weeks. All rats were sacrificed at 14 days after surgery, The pathological changes of the obstruction renal tissues were examined by hematoxylin-eosin staining and Masson staining. Immunohistochemistry and reverse transcription-polymerase chain reaction were applied to detect the protein and mRNA expression of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2. RESULTS AND CONCLUSION： Tetramethylpyrazine could significantly reduce the expansion and contraction of the tubular, the proliferation of renal interstitial fibrous tissue and inflammatory cell infiltration. Compared with sham-operation group, the protein and mRNA expression of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2 was significantly increased in model group （P 〈 0.01 ）. The protein and mRNA expression of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2 in tetramethylpyrazine group was smaller than that in the model group （P 〈 0.01 ）. Tetramethylpyrazineon could relieve the renal intersitial fibrosis by decreasing expression of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2.