迷迭香酸对大鼠系膜增生性肾小球肾炎肾内TGF-β1表达的影响
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江苏省科技厅社会发展基金(BS2003050)和南京市社会发展基金(200301093-3)资助


Protective effects of rosmarinic acid on experimental mesangioproliferative glomerulonephritis by reducing renal TGF-β1 expression
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    摘要:

    目的:探讨迷迭香酸(RA)对大鼠抗Thy1.1系膜增生性肾小球肾炎(MsPGN)的治疗作用及其对肾组织中转化生长因子β1(TGF-β1)表达的影响。方法:制备大鼠MsPGN模型,随机分为3组:模型组、低剂量及高剂量RA治疗组,另设正常对照组。治疗组每天分别给予迷迭香酸(25 mg/kg及50 mg/kg)灌胃,连续7天,隔日检测24 h尿蛋白总量。第8天处死大鼠并留取肾组织,PAS染色观察肾脏病理形态学改变,半定量RT-PCR及免疫组化方法检测大鼠肾皮质中TGF-β1的相对表达量。结果:免疫组化结果显示,正常大鼠TGF-β1少量表达于肾小球毛细血管袢及系膜区,模型组毛细血管袢及系膜区TGF-β1表达明显增多。两给药组肾小球TGF-β1表达量较模型组明显下降,24 h尿蛋白定量及病理改变较模型组均有明显改善;两给药组肾组织中TGF-β1 mRNA的相对表达量均小于模型组。结论:RA对大鼠MsPGN模型具有明显的保护作用,其机制可能部分与其抑制肾组织TGF-β1的过高表达有关。

    Abstract:

    Objective: To explore the effects of rosmarinic acid (RA) on experimental mesangioproliferative glomerulonephritis (MsPGN) and renal TGF-β1 expression. Methods: Rabbit antithymocyte serum(ATS) was produced, and then MsPGN animal models were prepared in Sprague-Dawley rats by a single intravenous injection of ATS. Twenty-four rats were randomly divided into four groups(n = 6, respectively): control group, treated with rabbit serum and tap water: model group, treated with ATS (10 ml/kg ) and tap water: low-dose and high-dose rosmarinic acid groups, treated with ATS(10 ml/kg ) and rosmarinic acid[25 mg/(kg·d)] and [25 mg/(kg·d), respectively]. Rosmarinic acid was administered by gavage for 7 days from the day of serum injection. Urinary protein was examined. All rats were sacrificed on the 8th day, then the kidneys were collected. The morphologic lesions were observed by PAS stain, and the expression of TGF-β1 was detected by semi-quantitative RT-PCR and immunohistochemistry. Results:Compared to model group, the level of 24-hour proteinuria in low-dose or high-dose rosmarinic acid treated groups decreased significantly. Renal pathologic changes in rosmarinic acid treated groups was also improved. Compared to normal group, glomerular expression of TGF-β1 mRNA was significantly increased in model group(P < 0.01), which was significantly inhibited by low-dose or high-dose rosmarinic acid. The expression of TGF-β1 mainly distributed along glomerular vessels and mesangiums. Compared to normal group, the expression of TGF-β1 was increased significantly in glomeruli of MsPGN rats. After 7 days of treatment, rosmarinic acid significantly down-regulated the expression of TGF-β1. Conclusion:Renoprotective mechanism of rosmarinic acid may partly be correlated with suppression on overexpression of TGF-β1 in renal tissue of MsPGN rats.

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赵三龙,黄松明,冯泉城,张爱华,郭 梅,丁桂霞,潘晓勤,费 莉,陈荣华.迷迭香酸对大鼠系膜增生性肾小球肾炎肾内TGF-β1表达的影响[J].南京医科大学学报(自然科学版),2006,(12):1168-1172

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  • 收稿日期:2006-05-29
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