镁络塞玛特 B 可改善 5/6 肾切除/梗塞大鼠的肾脏血液动力学，降低肾脏耗氧量。
Magnesium lithospermate B improves renal hemodynamics and reduces renal oxygen consumption in 5/6th renal ablation/infarction rats.
机构信息
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No.528 Zhangheng Road, Pudong District, Shanghai, 201203, People's Republic of China.
TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
出版信息
BMC Nephrol. 2019 Feb 12;20(1):49. doi: 10.1186/s12882-019-1221-5.
BACKGROUND
Magnesium lithospermate B (MLB) can promote renal microcirculation. The aim of the current project was to study whether MLB improves renal hemodynamics, oxygen consumption and subsequently attenuates hypoxia in rats induced by 5/6th renal Ablation/Infarction(A/I).
METHODS
Chronic renal failure (CRF) was induced in male SD rats by the 5/6 (A/I) surgery. 30 rats were randomly divided into three groups: sham group, 5/6 (A/I) + vehicle group (CRF group) and 5/6 (A/I) + MLB (CRF + MLB) group. 28 days after the surgery, rats were given with saline or 100 mg/kg MLB by i.p. injection for 8 weeks. The 24-h urinary protein (24hUp), serum creatinine (Scr), blood urine nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The protein expression of Fibronectin (FN), Collagen-I (Col-I), Connective Tissue Growth Factor(CTGF) and Interleukin-6 (IL-6) were measured by Western blot. Renal blood flow (RBF) and renal O consumption (QO) indicated as sodium reabsorption (QO/TNa) were detected before sacrifice. Renal hypoxia was assessed by measuring the protein expression of nNOS, HIF-1α and VEGF.
RESULTS
MLB significantly reduced 24hUp, Scr, BUN, SBP and DBP levels in rats with CRF. The expression of FN, Col-I, CTGF and IL-6 were down-regulated by MLB treatment in rats with CRF. In comparison to sham operated rats, 5/6 (A/I) rats had significantly lower RBF, and MLB significantly increased RBF in rats with CRF. Moreover, QO/TNa was higher in the CRF group as compared to that in the sham group, and it was significantly attenuated in the CRF + MLB group. MLB reversed the expression of nNOS (neuronal nitric oxide synthase), HIF-1α (hypoxia inducible factor-1) and VEGF in rats with CRF.
CONCLUSIONS
MLB improves renal function, fibrosis and inflammation in CRF rats induced by 5/6 (A/I), which is probably related to the increase in RBF, reduction of oxygen consumption and attenuation of renal hypoxia in the remnant kidney with CRF.
背景
镁 Lithospermate B (MLB) 可促进肾微循环。本研究旨在探讨 MLB 是否能改善肾血流量、氧耗量，进而减轻 5/6 肾切除/梗死（A/I）诱导的大鼠缺氧。
方法
雄性 SD 大鼠通过 5/6（A/I）手术诱导慢性肾衰竭（CRF）。30 只大鼠随机分为三组：假手术组、5/6（A/I）+载体组（CRF 组）和 5/6（A/I）+MLB 组（CRF+MLB 组）。手术后 28 天，大鼠腹腔注射生理盐水或 100mg/kg MLB，连续 8 周。测量 24 小时尿蛋白（24hUp）、血清肌酐（Scr）、血尿素氮（BUN）、收缩压（SBP）和舒张压（DBP）。采用 Western blot 法检测肾组织中纤维连接蛋白（FN）、I 型胶原（Col-I）、结缔组织生长因子（CTGF）和白细胞介素-6（IL-6）的蛋白表达。在处死前检测肾血流量（RBF）和肾耗氧量（QO），以钠重吸收（QO/TNa）表示。通过测量 nNOS、HIF-1α 和 VEGF 的蛋白表达来评估肾组织缺氧。
结果
MLB 可显著降低 CRF 大鼠的 24hUp、Scr、BUN、SBP 和 DBP 水平。与 CRF 大鼠相比，MLB 治疗可下调 FN、Col-I、CTGF 和 IL-6 的表达。与假手术大鼠相比，5/6（A/I）大鼠的 RBF 明显降低，而 MLB 可明显增加 CRF 大鼠的 RBF。此外，与假手术组相比，CRF 组的 QO/TNa 升高，而 CRF+MLB 组的 QO/TNa 明显降低。MLB 逆转了 CRF 大鼠中 nNOS（神经元型一氧化氮合酶）、HIF-1α（缺氧诱导因子-1）和 VEGF 的表达。
结论
MLB 可改善 5/6（A/I）诱导的 CRF 大鼠的肾功能、纤维化和炎症，这可能与 CRF 大鼠残肾 RBF 增加、氧耗量减少和肾组织缺氧减轻有关。
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