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胎盘间充质干细胞对胰腺创伤大鼠的保护作用OA北大核心CSTPCD

Protective effect of placental mesenchymal stem cells in the treatment of pancreatic trauma in rats

中文摘要英文摘要

目的 探讨胎盘间充质干细胞(P-MSCs)对胰腺创伤(PT)大鼠的保护作用.方法 健康成年雄性SD大鼠60只,随机分为对照组、胰腺创伤组(胰腺损伤区域及创伤周围局部注射1 ml PBS溶液)与P-MSCs组[胰腺损伤区域及创伤周围局部注射1 ml P-MSCs(1×106个/ml)],每组20只.采用400 kPa的致伤压强建立胰腺创伤大鼠模型.于术后1、3、5、7 d每组处死5只大鼠,收集血清及胰腺组织.HE染色观察胰腺组织病理学变化并进行病理损伤评分,ELISA法测定血清中淀粉酶(AMS)、脂肪酶(LPS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10、转化生长因子-β1(TGF-β1)浓度,以及胰腺组织中髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性,TUNEL法观察胰腺组织细胞凋亡情况.结果 与对照组比较,胰腺创伤组与P-MSCs组在胰腺创伤发生后腹腔积液量增加(P<0.05),胰腺/体重比、胰腺组织病理损伤总评分均升高(P<0.05),血清AMS、LPS、TNF-α、IL-6浓度及MPO活性早期升高,随时间延长呈下降趋势(P<0.05),而抗炎因子IL-10浓度及SOD活性随时间延长呈上升趋势(P<0.01),TGF-β1浓度早期下降,随时间延长呈上升趋势(P<0.01),凋亡指数(AI)明显升高(P<0.001).与胰腺创伤组比较,P-MSCs组大鼠胰腺组织大体形态得以改善,腹腔积液量减少(P<0.001),胰腺/体重比、胰腺组织病理损伤总评分降低(P<0.05),血清AMS、LPS、IL-6、TNF-α浓度及MPO活性更快恢复至正常水平(P<0.05),而抗炎因子IL-10、TGF-β1浓度及SOD活性升高速度增加(P<0.05),AI升高(P<0.001).结论 P-MSCs可促进PT大鼠组织修复,减轻其局部及全身炎症,改善组织氧化应激反应,促进胰腺腺泡细胞凋亡,对PT大鼠具有保护作用.

Objective To investigate the protective effect of placental mesenchymal stem cells(P-MSCs)on pancreatic trauma(PT)in rats.Methods Sixty healthy adult male SD rats were randomly divided into control group,pancreatic trauma group(inject 1 ml of PBS solution locally in the pancreatic injury area and around the trauma area),and P-MSCs group[inject 1 ml of P-MSCs(1×106/ml)locally in the pancreatic injury area and around the trauma area],with 20 rats in each group.The pancreatic trauma rat model was established using a traumatic pressure of 400 kPa.Five rats were sacrificed at 1,3,5,and 7 d after modeling in each group,and serum and pancreatic tissue were collected.HE staining was used to observe the pathological changes of pancreatic tissue and pathological scores were performed.The ELISA method was used to measure the concentrations of serum amylase(AMS),lipase(LPS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,and transforming growth factor-β1(TGF-β1),as well as the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)in pancreatic tissue.The TUNEL method was used to observe the level of apoptosis in pancreatic tissue was observed by the TUNEL method.Results Compared with control group,pancreatic trauma group and P-MSCs group showed significant differences after pancreatic trauma,including the generation of peritoneal fluid increased(P<0.05),the ratio of pancreas to body weight and the total score of pancreatic tissue pathological damage increased(P<0.05),and serum levels of AMS,LPS,TNF-α,IL-6,and MPO activity increased early and showed a decreasing trend over time(P<0.05),while anti-inflammatory factors IL-10 and SOD activity showed an increasing trend over time(P<0.01),level of TGF-β1 in the early decline showed an upward trend over time(P<0.01),and the apoptosis index(AI)significantly increased(P<0.001).Compared with pancreatic trauma group,P-MSCs group showed an improvement in the overall morphology of pancreatic tissue,the generation of peritoneal fluid decreased(P<0.001),the pancreas to body weight ratio and the total score of pancreatic tissue pathological damage decreased(P<0.05),and serum levels of AMS,LPS,IL-6,TNF-α and MPO activity returned to normal levels faster(P<0.05);and the rate of anti-inflammatory factors IL-10,TGF-β1 and SOD activity elevation increased(P<0.05),the AI increased(P<0.001).Conclusion P-MSCs can achieve therapeutic effects on pancreatic trauma in rats by promoting pancreatic tissue repair,reducing local and systemic inflammation,improving tissue oxidative stress,and enhancing pancreatic acinar cell apoptosis.

董鸿斐;黄茜;王张鹏;景光旭;史明;李先慧;孙红玉

西部战区总医院烧伤整形外科,四川成都 610083||西部战区总医院胰腺损伤与修复四川省重点实验室,四川成都 610083西部战区总医院烧伤整形外科,四川成都 610083||西部战区总医院基础实验室,四川成都 610083西部战区总医院胰腺损伤与修复四川省重点实验室,四川成都 610083||西部战区总医院基础实验室,四川成都 610083西部战区总医院胰腺损伤与修复四川省重点实验室,四川成都 610083西部战区总医院烧伤整形外科,四川成都 610083

临床医学

间充质干细胞胰腺创伤氧化应激凋亡

mesenchymal stem cellpancreatic traumaoxidative stressapoptosis

《解放军医学杂志》 2024 (004)

439-448 / 10

This work was supported by the General Program of National Natural Science Foundation of China(81772001),the Joint Military/Medicine Research Program of General Hospital of Western Theater Command(2019LH04),and the Incubation Project of Hospital Management Project of General Hospital of Western Theater Command(2021-XZYG-C36) 国家自然科学基金面上项目(81772001);西部战区总医院军事医学联合攻关项目(2019LH04);西部战区总医院院管课题孵化项目(2021-XZYG-C36)

10.11855/j.issn.0577-7402.0597.2023.1017

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