伊马替尼对单侧输尿管梗阻小鼠肾损伤的保护作用OA

Objective To investigate the protective effects of imatinib on renal injury in a mouse model of unilateral ureteral obstruction(UUO).Methods Seventy-two Kunming mice were randomly divided into three groups:the sham group(Sham,n=24),the UUO model group(UUO,n=24),and the imatinib treatment group(IM,n=24).In the Sham group,the ureter was freed but not ligated under anesthesia.In the UUO group,the ureter was freed and ligated.In the IM group,after ureter ligation,imatinib(50 mg/kg)was administered orally once daily starting from postoperative day 1 for 14 consecutive days.Blood samples were collected from the orbital sinus on postoperative days 3,7,and 14 to measure serum blood urea nitrogen(BUN)and serum creatinine(Scr)levels using the creatine kinase method,as well as serum interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)levels using ELISA.Renal tissues were harvested on postoperative days 3,7,and 14 for histopathological examination via hematoxylin-eosin(HE)and Masson staining,and protein expression levels of GRP78,PERK,PDGF-C,and PDGF-D were assessed by Western blot.Results Renal function tests showed that compared with the Sham group,serum BUN and Scr levels in the UUO group increased progressively on days 3,7,and 14(P<0.05).Compared with the UUO group,these levels were significantly reduced in the IM group on days 3 and 7(P<0.05),with a more pronounced decrease on day 14(P<0.001).Serum cytokine analysis revealed that IL-1β and TNF-α levels were significantly elevated in the UUO group at all time points compared with the Sham group(P<0.05),whereas the IM group exhibited significantly lower levels on days 3,7,and 14(P<0.05).HE staining showed that the UUO group exhibited glomerular atrophy,hyaline degeneration,tubular dilation,interstitial inflammatory cell infiltration,and disrupted capillary lumens with reduced numbers.In contrast,the IM group showed reduced renal injury,with histological features resembling those of the Sham group.Masson staining demonstrated a slight increase in collagen fibers in the UUO group on day 3,with significant collagen deposition and interstitial fibrosis on days 7 and 14.The IM group exhibited progressively increased tubular dilation and collagen fiber content with prolonged obstruction,but the degree of interstitial fibrosis was alleviated.Western blot analysis showed that compared with the Sham group,GRP78 and PERK expression levels were significantly upregulated in the UUO group on days 7 and 14(P<0.05),while PDGF-C and PDGF-D expression levels were markedly downregulated(P<0.05).In the IM group,GRP78 and PERK expression levels were significantly reduced on days 7 and 14(P<0.05),whereas PDGF-C and PDGF-D expression levels were significantly upregulated(P<0.05).Conclusion Imatinib exerts a protective effect against renal injury,likely through the inhibition of apoptosis and inflammatory cytokine production,as well as the regulation of en-doplasmic reticulum stress.