关键词: 骨髓间充质干细胞, 外泌体, 顺铂, 急性肾损伤, 细胞凋亡

Abstract: Ｏｂｊｅｃｔｉｖｅ：To explore the role and mechanism of bone marrow mesenchymal stem cells-derived exosomes （BMSC-exos） in protecting against cisplatin （CDDP）-induced acute kidney injury （AKI）.
Ｍｅｔｈｏｄｏｌｏｇｙ：48 C57BL／6 mice were randomly divided into 4 groups: control （CN） group，cisplatin-induced AKI model （CDDP） group，CDDP+BMSC-exos （CDDP+EXO） group，and CDDP+EXO+PI3K inhibitor （LY294002） （CDDP+EXO+LY294002） group. Saline，cisplatin，cisplatin+BMSC-exos and cisplatin+BMSC-exos+LY294002 were injected intraperitoneally or Caudal vein，respectively. blood was retained for measurement of creatinine （SCr） and urea nitrogen （BUN）； renal tissues were taken for pathological analyses； renal tubular epithelial cells （RTEC） were observed for apoptosis by TUNEL； and immunohistochemical staining was performed to detect Cleaved caspase-3，GRP-78，caspase-12 and CHOP expression localisation； Cleaved caspase-3，GRP-78，caspase-12，CHOP，PI3K and p-AKT expression were determined by Western Blot.
Ｒｅｓｕｌｔｓ：In the CDDP-induced AKI model，the number of TUNEL-positive cells in renal tissues was significantly increased （P<0.05），and the area of immunohistochemically immunised Cleaved caspase-3，GRP-78，caspase-12 and CHOP positivity was significantly increased （P<0.05），and the Western Blot method confirmed the expression of Cleaved caspase-3，GRP-78，caspase-12 and CHOP expression levels were significantly up-regulated （P<0.05），and p-AKT expression levels were significantly down-regulated （P<0.05）； the number of TUNEL-positive cells in renal tissues was significantly reduced by treatment with BMSC-exos （P<0.05），and the number of immunohistochemistry-immunoconjugated Cleaved caspase-3，GRP-78，caspase-12 and CHOP positive area was significantly reduced （P<0.05），Western Blot method confirmed that Cleaved caspase-3，GRP-78，caspase-12 and CHOP expression levels were significantly down-regulated （P<0.05），and the p-AKT expression level were significantly up-regulated （P<0.05）； the number of TUNEL-positive cells in renal tissues was significantly increased （P<0.05），and the immunohistochemical immunoconjugate area of Cleaved caspase-3，GRP-78，caspase-12 and CHOP positivity was significantly increased （P<0.05） with the application of LY294002 prior to the treatment of BMSC-exos. Western Blot method confirmed that Cleaved caspase-3，GRP-78，caspase-12 and CHOP expression levels were significantly up-regulated （P<0.05） and p-AKT expression levels were significantly down-regulated （P<0.05）.
Ｃｏｎｃｌｕｓｉｏｎ：The mechanism of CDDP-AKI protection by BMSC-exos may be achieved by inhibiting Endoplasmic reticulum stress and activating PI3K／Akt signalling pathway.

Key words: bone marrow mesenchymal stem cells, exosomes, cisplatinacute kidney injury, cell apoptosis