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1.610031 成都,西南交通大学医学院临床医学系
2.610083 成都,西部战区总医院普通外科
[戴睿武,E-mail:dairuiwu@swjtu.edu.cnDAI Ruiwu, E-mail: dairuiwu@swjtu.edu.cn
收稿:2022-01-19,
修回:2022-02-21,
纸质出版:2022-08-30
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韩丽, 陈思平, 赵治戎, 等. 脐带间充质干细胞来源的外泌体对大鼠创伤性胰腺炎损伤的修复[J]. 陆军军医大学学报, 2022,44(16):1642-1650.
Li HAN, Siping CHEN, Zhirong ZHAO, et al. The repair effect of exosomes derived from human umbilical cord mesenchymal stem cells on traumatic pancreatitis in rats[J]. Journal of Army Medical University, 2022, 44(16): 1642-1650.
韩丽, 陈思平, 赵治戎, 等. 脐带间充质干细胞来源的外泌体对大鼠创伤性胰腺炎损伤的修复[J]. 陆军军医大学学报, 2022,44(16):1642-1650. DOI: 10.16016/j.2097-0927.202201171.
Li HAN, Siping CHEN, Zhirong ZHAO, et al. The repair effect of exosomes derived from human umbilical cord mesenchymal stem cells on traumatic pancreatitis in rats[J]. Journal of Army Medical University, 2022, 44(16): 1642-1650. DOI: 10.16016/j.2097-0927.202201171.
目的
2
探讨脐带间充质干细胞(human umbilical cord mesenchymal stem cells,hUC-MSCs) 来源的外泌体(hUC-MSCs exosome,hUCMSC-Ex)对创伤性胰腺炎的治疗和保护作用。
方法
2
60只成年雄性健康SD大鼠(体质量200~250 g),通过随机区组法分为4组(
n
=15): 对照组(Control组),开腹后轻轻翻动胰腺,随后关腹,经尾静脉注射1 mL生理盐水;创伤性胰腺炎组(TP组),使用造模仪建立创伤性胰腺炎大鼠模型,经尾静脉注射1 mL生理盐水;TP+hUC-MSCs组(造模后经尾静脉注射干细胞)和TP+hUCMSC-Ex组(造模后经尾静脉注射外泌体)。采用超速离心法获取外泌体,使用透射电镜对外泌体进行形态学鉴定;HE染色观察胰腺组织损伤的程度;ELISA法检测淀粉酶、脂肪酶、促炎因子、抗炎因子的表达水平;原位末端标记法(TUNEL)检测细胞凋亡情况;Western blot检测细胞凋亡蛋白Bax、Caspase-3表达水平。
结果
2
与TP组比较,TP+hUC-MSCs组和TP+hUCMSC-Ex组的胰腺组织病理学评分明显降低(
P
<
0.05),血清淀粉酶、脂肪酶浓度、IL-6、TNF-α表达水平明显降低(
P
<
0.05),而IL-10、TGF-β表达水平明显升高(
P
<
0.05)。TP组的凋亡指数明显高于对照组(
P
<
0.05),而TP+
hUC-MSCs组和TP+hUCMSC-Ex组的凋亡指数显著低于TP组(
P
<
0.05),且TP+hUC-MSCs组和TP+hUCMSC-Ex组的凋亡蛋白Bax、Caspase-3表达水平明显降低(
P
<
0.05)。
结论
2
hUCMSC-Ex可以通过控制全身性的炎症反应和抑制大鼠腺泡细胞凋亡,参与胰腺组织再生修复。
Objective
2
To explore the curative and protective effects of exosomes derived from human umbilical cord mesenchymal stem cells(hUCMSC-Ex)on traumatic pancreatitis in rats.
Methods
2
Sixty grown male SD rats (200~250 g) were selected and randomly divided into four groups (
n
=15 of each group): control
traumatic pancreatitis (TP)
TP+hUC-MSCs
and TP+hUCMSC-Ex groups. In the control group
the pancreas was gently turned over after laparotomy. Subsequently
the abdomen was closed and 1 mL normal saline was injected via the tail vein. In the TP group
a rat model of TP was established using a model impactor and 1 mL of normal saline was injected
via
the tail vein. hUC-MSCs or hUCMSC-Ex were injected
via
tail vein after modeling in TP+hUC-MSCs and TP+hUCMSC-Ex groups. The ultracentrifugation was used to obtain exosomes
and transmission electron microscopy was used to identify exosomes; HE staining was used for detecting the severity of damage of pancreatic tissue; The expression levels of amylase
lipase
pro-inflammatory factors and anti-inflammatory factors were detected by ELISA; Cell apoptosis was detected by TUNEL; The expression levels of apoptosis proteins Bax and Caspase-3 were detected by Western blotting.
Results
2
Compared with TP group
TP+hUC-MSCs group and TP+hUCMSC-Ex group had obvious lower score on pancreas histopathological scoring(
P
<
0.05); The concentrations of serum amylase and lipase were significantly decreased (
P
<
0.05); The expression levels of serum pro-inflammatory factors IL-6 and TNF-α were significant
ly decreased
while the expression levels of anti-inflammatory factors IL-10 and TGF-β were significantly increased (
P
<
0.05); The apoptotic index in the TP group was significantly higher than that of in the control group (
P
<
0.05)
and the apoptotic index in the TP+hUC-MSCs group and TP+hUCMSC-Ex group was significantly lower than that in the TP group (
P
<
0.05). Compared with TP group
the expression levels of pancreatic apoptotic proteins Bax and Caspase-3 were significantly decreased in the TP+hUC-MSCs group and TP+hUCMSC-Ex group (
P
<
0.05).
Conclusion
2
The hUCMSC-Ex can inhibit the apoptosis of rat acinar cells and participate in the regeneration and repair of pancreatic tissue by controlling the systemic inflammatory reaction.
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