In the current study, we showed that MLB improved renal function and attenuated renal fibrosis and inflammation in the 5/6 (A/I) rat model of CRF, which was correlated with the increase in renal blood flow and reduction in remnant renal oxygen consumption (QO2/TNa). Moreover, MLB reversed the expression of nNOS, HIF-1α and VEGF protein in the kidney of 5/6 (A/I) rats.
The kidney is one of the major organs with well-supplied oxygenated blood, and it is vulnerable to ischemic insults leading to impaired renal function [
3].The ischemic conditions can be induced by acute kidney injuries and by damages associated with chronic kidney diseases [
13]. Hypoxia, resulting from decreased blood flow or increased oxygen consumption, affects the expression of a wide array of genes, including many fibrogenic factors, leading to the progressive loss of renal function [
4,
14,
15].MLB exerts beneficial effects in several rodent models of chronic kidney disease, and the protective mechanism of MLB in the kidney is related to its anti-oxidative and anti-fibrotic potentials [
7‐
9]. It has been shown that MLB promoted renal circulatory state in healthy rat kidneys and adenine induced CKD kidneys [
11,
15]. We therefore hypothesized that MLB protects renal function in chronic kidney disease through improving renal hemodynamics and subsequently attenuating hypoxia in 5/6 kidneys. In our study, we firstly showed that MLB attenuated renal function decline, renal fibrosis and inflammation in the 5/6 (A/I) rat model of renal failure. Secondly, we showed that MLB significantly increased renal blood flow. To further confirm that the renal hypoxia was reduced by MLB, we measured the expression of HIF-1α, the hypoxia marker, in the kidney tissues [
5]. We found that MLB reduced the expression of HIF-1αin 5/6 rat kidneys suggesting that renal hypoxia was attenuated by MLB. Moreover, we measured the expression of VEGF which is a downstream target of HIF-1α in 5/6 and the renal expression of VEGF is tightly regulated by hypoxia [
16] Our study showed that the renal expression of VEGF in CRF rats was reduced by the MLB treatment. Interestingly, in the present study, we found that MLB reduced renal oxygen consumption in 5/6 (A/I) rats. We further measure the expression of nNOS, a negative regulator of oxygen utilization in mitochondria, and we found that MLB restored the expression of nNOS in 5/6 (A/I) rat kidneys [
4].