Abstract
BackgroundMagnesium 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).MethodsChronic 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 O2 consumption (QO2) indicated as sodium reabsorption (QO2/TNa) were detected before sacrifice. Renal hypoxia was assessed by measuring the protein expression of nNOS, HIF-1α and VEGF.ResultsMLB 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, QO2/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.ConclusionsMLB 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.
Highlights
Magnesium lithospermate B (MLB) can promote renal microcirculation
We aimed to study whether MLB improves renal hypoxia and protects renal function in 5/6 ablation/infarction (A/I) rats through ameliorating renal hemodynamics and attenuating renal oxygen consumption
The renal ablation/infarction (A/I) model of chronic kidney disease (CKD) was established in male SD rats weighted 190–210 g, which were randomly divided into three groups: (I) sham operation, (II) 5/6 renal ablation/ infarction (A/I) operation, (III) 5/6 A/I operation +Magnesium Lithospermate B (MLB). 28 days after the operation, rats were treated with vehicle or 100 mg/kg MLB by i.p. once daily for 8 weeks
Summary
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). In CKD rats induced by 5/6thnephrectomy, MLB improved renal function as shown by decreased serum creatinine (Scr) and blood urea nitrogen (BUN) levels, which was correlated with reduced mesangial proliferation, tubulointerstitial lesions and glomerular sclerotic lesions [7, 8]. In streptozotocin-induced diabetic rats, MLB displayed a reno-protective property as shown by reduced microalbuminuria, glomerular hypertrophy, and mesangial expansion. These beneficial effects of MLB in diabetic kidneys was associated with decreased expression of renal malondialdehyde (MDA), TGF-β1, fibronectin, and collagen [9]. MLB increased renal blood flow in adenine induced CKD rats [11] It is not known whether MLB improves renal hypoxia through ameliorating renal microcirculatory system in diseased kidneys
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