关键词: 间充质基质细胞, 干细胞移植, NLR家族, 热蛋白结构域包含蛋白3, 肾纤维化, 肾动脉途径移植干细胞

Abstract: Objective To observe the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) transplanted by different ways on chronic kidney disease (CKD) rats and the effect of nucleotide binding oligomerized domain-like receptor protein 3 (NLRP3) inflammasome on renal fibrosis. Methods There were 50 male SD rats in this study, of which 2 were used to isolate and culture BMSCs in vitro. After successful CKD modeling (left nephrectomy+multiple tail vein injection of doxorubicin), thirty-six rats were randomly divided into following groups: the model group (CKD group), the renal artery transplantation of BMSCs group (A-M group) and the tail vein transplantation of BMSCs group (V-M group). The normal control group (SHAM group, n=12) was given 0.9%NaCl by caudal vein infusion. The serum levels of creatinine, urea nitrogen and 24 h urinary protein were measured at 7 d and 14 d after BMSCs transplantation. HE staining and Masson tricolor staining were performed to observe the pathological structure changes and fibrosis of the kidney. Immunohistochemical staining was performed to observe the expression levels of NLRP3, apoptosis-related microprotein (ASC) and cysteine aspartate proteinase-1 (Caspase-1). Results Compared with SHAM group, the serum creatinine, urea nitrogen and 24 h urinary protein were significantly increased on day 7 and day 14 in the CKD group, A-M group and V-M group (P＜0.05). On 7 and 14 days after BMSCs transplantation, the serum creatinine, urea nitrogen and 24 h urinary protein were significantly lower in the A-M group and the V-M group than those in the CKD group, and the A-M group was lower than those in the V-M group (P＜0.05). HE staining and Masson staining showed that the inflammatory infiltration, the number of atrophic glomeruli, the dilatation of renal tubules and the degree of fibrosis were reduced in the A-M group and V-M group compared with those of the CKD group. The improvement degree in the A-M group was better than that in the VM group. Immunohistochemical results showed that the expression levels of NLRP3, ASC and Caspase-1 in renal interstitium of rats were decreased in the A-M group and V-M group compared with those in the CKD group, and the decrease was better in the A-M group than that in the V-M group. Conclusion BMSCs can improve the renal fibrosis in CKD rats. The arterial approach is better than the venous approach in the observation period. Its mechanism may be related to the inhibition of NLRP3 inflammasome activation.

Key words: mesenchymal stromal cells, stem cell transplantation, NLR family, pyrin domain-containing 3 protein, renal fibrosis, renal arterial approach transplantation of stem cells