Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear ...Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.展开更多
目的:通过破骨细胞分化传导通路OPG-RANKL-RANK中的骨保护素(Osteoprotegrin,OPG)、破骨细胞分化因子(receptor activator of nuclear factor kappa B ligand,RANKL)蛋白及基因表达探讨运动防治骨质疏松的机理。方法:大鼠随机分为正常...目的:通过破骨细胞分化传导通路OPG-RANKL-RANK中的骨保护素(Osteoprotegrin,OPG)、破骨细胞分化因子(receptor activator of nuclear factor kappa B ligand,RANKL)蛋白及基因表达探讨运动防治骨质疏松的机理。方法:大鼠随机分为正常对照组、假手术组、模型组、阳性对照组和运动组。模型组、阳性对照组和运动组大鼠摘除双侧卵巢,假手术组切除小块脂肪组织。1个月后运动组进行中等强度运动;阳性对照组大鼠灌服已烯雌酚,正常对照组、假手术组、模型组和运动组大鼠灌服等容积蒸馏水。持续干预3个月后检测胫骨骨组织形态计量学指标,成骨细胞和骨髓基质细胞的OPG、RANKL蛋白及mRNA表达。结果:与模型组相比,阳性对照组和运动组骨小梁体积百分比(TBV%)、OPG蛋白及mRNA表达显著升高(P<0.05);骨小梁吸收表面百分比(TRS%)、骨小梁形成表面百分比(TFS%)、活性生成表面百分比(AFS%)、骨小梁矿化率(MAR)、骨小梁骨生成率(BFR)、类骨质平均宽度(OSW)、骨皮质矿化率(mAR)、成骨细胞/骨髓基质细胞(OB/MSC)RANKL蛋白及mRNA表达显著降低(P<0.05);模型组各指标与假手术组相比均有显著性差异(P<0.05)。结论:运动对去卵巢大鼠骨组织形态计量相关指标有一定的改善作用,对破骨细胞分化传导通路OPGRANKL-RANK中的OPG、RANKL蛋白及基因表达有一定调节作用,并对去卵巢所致大鼠骨质疏松症有一定的防治作用。展开更多
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2022D01C604)。
文摘Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.
文摘目的:通过破骨细胞分化传导通路OPG-RANKL-RANK中的骨保护素(Osteoprotegrin,OPG)、破骨细胞分化因子(receptor activator of nuclear factor kappa B ligand,RANKL)蛋白及基因表达探讨运动防治骨质疏松的机理。方法:大鼠随机分为正常对照组、假手术组、模型组、阳性对照组和运动组。模型组、阳性对照组和运动组大鼠摘除双侧卵巢,假手术组切除小块脂肪组织。1个月后运动组进行中等强度运动;阳性对照组大鼠灌服已烯雌酚,正常对照组、假手术组、模型组和运动组大鼠灌服等容积蒸馏水。持续干预3个月后检测胫骨骨组织形态计量学指标,成骨细胞和骨髓基质细胞的OPG、RANKL蛋白及mRNA表达。结果:与模型组相比,阳性对照组和运动组骨小梁体积百分比(TBV%)、OPG蛋白及mRNA表达显著升高(P<0.05);骨小梁吸收表面百分比(TRS%)、骨小梁形成表面百分比(TFS%)、活性生成表面百分比(AFS%)、骨小梁矿化率(MAR)、骨小梁骨生成率(BFR)、类骨质平均宽度(OSW)、骨皮质矿化率(mAR)、成骨细胞/骨髓基质细胞(OB/MSC)RANKL蛋白及mRNA表达显著降低(P<0.05);模型组各指标与假手术组相比均有显著性差异(P<0.05)。结论:运动对去卵巢大鼠骨组织形态计量相关指标有一定的改善作用,对破骨细胞分化传导通路OPGRANKL-RANK中的OPG、RANKL蛋白及基因表达有一定调节作用,并对去卵巢所致大鼠骨质疏松症有一定的防治作用。
