| Acute kidney injury(AKI) is a kind of common kidney disease in clinic. The therapeutic action of bone marrow-derived mesenchymal stem cells(BMSCs) in AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation, and only small amount of cells could migrate into the kidney tissue. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. Therefore, how to develope novel therapy models to improve the therapeutic action of BMSCs against AKI, is a problem that should be solved quickly in this field. Muscone holds the anti-apoptotic and anti-oxidative stress potential. The proliferation, secretion and migration ability of BMSCs could also be enhanced by the compound. However, whether muscone could be combined with BMSCs in the treatment of AKI and further refine the therapeutic action of BMSCs treatment, is still unclear. Therefore, in this study, we mainly analyzed and explored the problem through the research in vitro and in vivo.In our study, the rat BMSCs and renal tubular epithelial cells(RTECs) were isolated from rat bone marrow and kidney tissue. After being characterized, muscone in different concentration(0.0 mg/L, 0.3 mg/L, 1.0 mg/L and 3.0 mg/L) was used to treat rat BMSCs and RTECs, to evaluate the effect of muscone on cell proliferation and section. Then, gentamicin was used to establish rat AKI model in vivo, and the AKI model was treated wih muscone and BMSCs. In this study, normal group, model group, positive drug group(Dexamethasone was used as the positive drug herein), muscone group, BMSCs group and combined group(BMSCs combined with muscone) were designed respectively. After 1-week treatment, the kidney weight index, the biochemical variables associated with kidney function and pathologicalchanges were detected to compare the therapy effect in different groups. Meanswhile, the assistant effect of Muscone on the therapeutic action of BMSCs against AKI was also evalusted on the sides of anti-apoptosis, anti-inflammation and cell migration. Our results indicated that the rat BMSCs and RTECs hold normal cell phenotypes and BMSCs also hold osteogenic differentiation ability and adipogenic differentiation ability. With the treatment of muscone, the proliferation ability of BMSCs was improved obviously(P﹤0.05), as well as the BMP7 secretion ability(P﹤0.05). However, muscone showed little effect on the proliferation and secretion of RTECs. In the AKI model group induced with gentimacin, the kidney index was up-regulated and many biochemical variables associated with kidney function were disturbed in blood and urine. Notable damage, dilatation, and effusion in the kidney tubules and collecting tubules existed in kidney tissue. With the treatment of dexamethasone, muscone and BMSCs, those symptoms were relieved in different degree. Especially for the kidney weight index and some biochemical variables, the combined group hold better therapeutic action(P﹤0.05). On the side of anti-apoptosis, the combined group showed better effect compared with BMSCs group and muscone group, which was demonstrated by Tunel staining, and the expression of some apoptisis genes(Caspase 3 and Bax) also kept lower in the combined group(P﹤0.05). On the side of anti-inflammation, nearly every group showed the ability to inhibit the expression of some inflammatory factors, MCP-1, IL-10, RANTES and MIP-2. The combined group hold lower expression of the RANTES and MIP-2, compared with BMSCs group and muscone group, indicating the advantage of the combined group on the treatment of AKI. In addition, the trans-well experiment indicated that BMSCs in the combined group hold better migration ability(P﹤0.05), and this ability was also demonstrated by the research in vivo, and the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration.In total, based on the biotherapy function of BMSCs against AKI, this study mainly indicated that the enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential. Compared with single BMSCs or muscone therapy,the combined group hold better therapeutic effect against AKI, and further developed a new therapeutic strategy for the treatment of AKI, avoiding the toxic and side effects of the traditional drug therapy, the limitance of single BMSCs therapy and other problems. For the easy operation of BMSCs culture and the clinical application of muscone, the novel therapy model against AKI could hold obvious significance in the clinical application. |
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