Research on mechanism of MAPK signal pathway induced by BMSCs for the proteinuria of rat's kidney, glomerulosclerosis and activity of RAS.

OBJECTIVE: The aim of the article was to explore the mechanism of MAPK (Mitogen-activated protein kinase) signal pathway induced by BMSCs (Bone marrow mesenchymal stem cells) for the proteinuria of rat's kidney, glomerulosclerosis and activity of RAS (Renin angiotensin) system. MATERIALS AND METHODS: Thirty rats were divided into sham group, FSGS (Focal Segmental Glomerular Sclerosis) group and BMSCs group. The variation of biochemical criterion and protein of rats in the three groups was compared. The variation condition of rats' kidney and GSI (Glomerular sclerosis index), ECM/GA (Extracellular matrix/glomerular area) was compared. The activity of RAS was analyzed. Finally, the p38 MAPK and p-p38 MAPK protein was compared. RESULTS: Compared with sham group rats, the SCr, BUN and proteinuria after twenty-four hours in FSGS group was improved. The blood albumin was notably reduced. At the same time, there was evident deterioration in the pathology of nephridial tissue (p<0.05). The biochemical criterion in transplanted BMSCs group was significantly reduced. At the same time, the blood albumin and pathology of nephridial tissue was also improved (p<0.05). The glomerulus in sham group was normal. There was abundant induration for the glomerulus in FSGS group compared with sham group. The relative value of GSI and ECM/GA was higher than in sham group (p<0.05). The relative value of GSI and ECM/GA in BMSCs group was reduced notably compared with FSGS group (p<0.05). The activity of RAS in FSGS group was enhanced. But activity of RAS in BMSCs group was remarkably restrained. The p38 MAPK and p-p38 MAPK protein in FSGS group was significantly increased compared with the other groups (p<0.05). The protein expression in BMSCs group and inhibitor group was restrained (p<0.05). CONCLUSIONS: The BMSCs could restrain the proteinuria of rat's kidney and activity of RAS and they were related with the expression of MAPK signal pathway closely.

Zhi-Long-Huo-Xue-Tong-Yu modulates mitochondrial fission through the ROCK1 pathway in mitochondrial dysfunction caused by streptozotocin-induced diabetic kidney injury.

Zhi-Long-Huo-Xue-Tong-Yu (ZLHXTY) is a defined mixture of 5 herbs developed by Professor S.J. Yang according to the Buyang Huanwu decoction method, which has been recorded in the Yilingaicuo. This study investigated the renoprotective effects of ZLHXTY on mitochondrial dysfunction induced by diabetic kidney injury in a diabetic rat model. Diabetes was induced by a single intravenous injection of streptozotocin. Rats were daily fed either ZLHXTY or vehicle beginning in the 1st week after injection. Levels of mitofusin 2 (mfn2), dynamin-related protein 1 (Drp1), caspase-9, and rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were detected using Western blotting. Levels of intracellular calcium and adenosine triphosphate (ATP) were examined using an enzyme-linked immunosorbent assay. An electron microscopic examination of kidney tissue was performed. The levels of mfn2 and ATP in the diabetes and ZLHXTY groups decreased from the 4th week after modeling. The expression levels of Drp1, ROCK1, and caspase-9 increased in the diabetes group but decreased in the ZLHXTY group from the 4th week after modeling. Compared with the diabetes group, ZLHXTY treatment decreased the mesangial expansion index and proteinuria levels, and improved the pathological changes typical of diabetic kidney injury. Furthermore, ZLHXTY treatment inhibited the activation of ROCK1 and expression of Drp1 and caspase-9, but did not affect the expression of mfn2. This study indicates that ZLHXTY treatment could protect kidney tissue from diabetic injury through the ROCK1 pathway response to mitochondrial dysfunction induced by diabetes.