
浏览全部资源
扫码关注微信
400010 重庆,陆军特色医学中心肾内科
[何娅妮,E-mail: heynmail@163.com HE Yani, E-mail: heynmail@163.com
收稿:2021-02-23,
修回:2022-05-25,
纸质出版:2022-11-30
移动端阅览
汪晓月, 蔡青利, 喻芳, 等. 骨髓间充质干细胞外泌体治疗改善高糖腹透液引起的小鼠腹膜纤维化[J]. 陆军军医大学学报, 2022,44(22):2291-2299.
Xiaoyue WANG, Qingli CAI, Fang YU, et al. Exosomes derived from bone marrow mesenchymal stem cells ameliorate peritoneal fibrosis induced by high glucose peritoneal dialysate solution in mice[J]. Journal of Army Medical University, 2022, 44(22): 2291-2299.
汪晓月, 蔡青利, 喻芳, 等. 骨髓间充质干细胞外泌体治疗改善高糖腹透液引起的小鼠腹膜纤维化[J]. 陆军军医大学学报, 2022,44(22):2291-2299. DOI: 10.16016/j.2097-0927.202202132.
Xiaoyue WANG, Qingli CAI, Fang YU, et al. Exosomes derived from bone marrow mesenchymal stem cells ameliorate peritoneal fibrosis induced by high glucose peritoneal dialysate solution in mice[J]. Journal of Army Medical University, 2022, 44(22): 2291-2299. DOI: 10.16016/j.2097-0927.202202132.
目的
2
探讨骨髓间充质干细胞(bone marrow mesenchyml stem cell
BMSCs)来源的外泌体在高糖腹透液诱导的小鼠腹膜纤维化中的作用。
方法
2
选取32只6~8周龄的C57bl/6雄鼠,随机分为为4组(
n
=8):正常对照组、生理盐水组、4.25%腹膜透析液组、4.25%腹膜透析液+外泌体组。建立高糖腹透液诱导的腹膜纤维化小鼠模型,42 d后处死小鼠并收集标本。通过改良腹膜平衡实验(peritoneal balance test
PET)检测小鼠腹膜功能;免疫组化法检测小鼠腹膜纤维化标志物的表达;实时定量PCR法检测小鼠腹膜纤维化因子mRNA的表达;ELISA法检测小鼠促纤维化因子的表达。
结果
2
4.25%腹膜透析液组与对照组小鼠比较,腹膜间皮下区域厚度明显增加(
P
<
0.01);4.25%腹膜透析液组腹膜纤维化标志物(α-SMA、Collagen-Ⅰ、Collagen-Ⅲ)表达显著增强,而4.25%腹膜透析液+外泌体组的腹膜纤维化标志物表达显著低于4.25%腹膜透析液组(
P
<
0.01)。4.25%腹膜透析液+外泌体组小鼠相较4.25%腹膜透析液组的超滤功能显著改善(
P
<
0.05)。qRT-PCR结果显示,与4.25%腹膜透析液组比较,4.25%腹膜透析液+外泌体组腹膜促纤维化因子TGF-β1(转化生长因子-β1)水平明显降低(
P
<
0.05)。
结论
2
BMSCs来源的外泌体可有效减轻高糖腹透液诱导的小鼠腹膜纤维化。BMSCs来源的外泌体治疗可能成为抑制腹膜纤维化的新方法。
Objective
2
To investigate the role of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) in peritoneal fibrosis induced by high glucose peritoneal dialysis in mice.
Methods
2
Thirty-two male C57bl/6 mice were randomly divided into 4 groups: the normal control
the saline
the 4.25% peritoneal dialysate and the 4.25% peritoneal dialysate+exosome group. A mouse model of peritoneal fibrosis induced by high glucose peritoneal dialysis was established. The mice were sacrificed after 42 d and the specimens were collected. Peritoneal function was detected by modified peritoneal balance test (PET); The expression of peritoneal fibrosis markers was detected by immunohistochemical method; The expression of peritoneal fibrosis factor mRNA was detected by real-time quantitative PCR
and the expression of pro-fibrotic factor was detected by ELISA.
Results
2
Compared with the normal control group
the 4.25% peritoneal dialysis group had obviously increased thickness of sub
cutaneous area of peritoneal mesothelium (
P
<
0.01). The expression of peritoneal fibrosis markers (α-SMA
collagen-Ⅰ and Collagen-Ⅲ) was significantly increased in the 4.25% peritoneal dialysate group
while the expression of peritoneal fibrosis markers in the 4.25% peritoneal dialysate+exosome group was significantly lower than that in the 4.25% peritoneal dialysate group
(P
<
0.01). Compared with the 4.25% peritoneal dialysate+exosome group
the ultrafiltration function of mice in the 4.25% peritoneal dialysate+exosome group was significantly improved (
P
<
0.05). qRT-PCR results showed that the level of peritoneal fibrosis promoting factor TGF-β1 in the 4.25% peritoneal dialysate+exosome group was significantly lower than that in the 4.25% peritoneal dialysate+exosome group (
P
<
0.05).
Conclusion
2
Exosomes derived from BMSCs can effectively reduce peritoneal fibrosis induced by high glucose peritoneal dialysis solution in mice. Exosomes derived from BMSCs may be a new method to inhibit peritoneal fibrosis.
THURLOW J S, JOSHI M, YAN G F, et al . Global epidemiology of end-stage kidney disease and disparities in kidney replacement therapy[J ] . Am J Nephrol, 2021, 52(2): 98-107. DOI: 10.1159/000514550.
MORINELLI T A, LUTTRELL L M, STRUNGS E G, et al . Angiotensin Ⅱ receptors and peritoneal dialysis-induced peritoneal fibrosis[J ] . Int J Biochem Cell Biol, 2016, 77(Pt B): 240-250. DOI: 10.1016/j.biocel.2016.04.016.
ALATAB S, NAJAFI I, ATLASI R, et al . A systematic review of preclinical studies on therapeutic potential of stem cells or stem cells products in peritoneal fibrosis[J ] . Italian J Urol Nephrol, 2018, 70(2): 162-178. DOI: 10.23736/S0393-2249.17.02882-X.
李清茹, 张琳琪, 陈旭, 等. 间充质干细胞来源细胞外囊泡治疗和修复急慢性肾损伤[J]. 中国组织工程研究, 2022, 26(31): 5069-5075.
LI Q R, ZHANG L Q, CHEN X, et al . Mesenchymal stem cells-derived extracellular vesicles in the treatment and repair of acute and chronic renal injuries[J ] . Chin J Tissue Eng Res, 2022, 26(31): 5069-5075.
程娇娇, 崔钧贺, 高永胜, 等. 外泌体在远隔缺血预适应中对神经细胞的保护作用[J]. 生理科学进展, 2020, 51(3): 216-218.
CHENG J J, CUI J H, GAO Y S, et al . Effect of exosomes on neurocytes protection in remote ischemic preconditioning[J ] . Prog Physiol Sci, 2020, 51(3): 216-218.
项协隆, 林沁. 腹膜纤维化大鼠模型研究进展[J]. 医学综述, 2010, 16(10): 1445-1447.
XIANG X L, LIN Q. Advances in peritoneal fibrosis rat model[J]. Med Recapitul, 2010, 16(10): 1445-1447.
JIE S, YUCHEN Z, ZHIFANG N, et al . Mesenchymal stem cell-derived small extracellular vesicles in the treatment of human diseases: progress and prospect[J ] . World J Stem Cells. 2021 Jan 26;13(1): 49-63. doi: 10.4252/wjsc.v13.i1.49.
程欢, 苏盖, 陶思跃, 等. 小鼠骨髓间充质干细胞的稳定高效培养及外泌体的提取[J]. 安徽医科大学学报, 2020, 55(4): 518-522. DOI: 10.19405/j.cnki.issn1000-1492.2020.04.007.
CHENG H, SU G, TAO S Y, et al . Stable and efficient culture of mouse bone marrow mesenchymal stem cells and extraction of its exosomes[J ] . Acta Univ Med Anhui, 2020, 55(4): 518-522. DOI: 10.19405/j.cnki.issn1000-1492.2020.04.007.
KHATUN Z, BHAT A, SHARMA S, SHARMA A, et al . Elucidating diversity of exosomes: biophysical and molecular characterization method s[J ] . Nanomedicine (Lond). 2016 Sep; 11(17): 2359-2377.
EBRAHIM N, AHMED I A, HUSSIEN N I, et al . Mesenchymal stem cell-derived exosomes ameliorated diabetic nephropathy by autophagy induction through the mTOR signaling pathway[J ] . Cells, 2018, 7(12): E226. DOI: 10.3390/cells7120226.
蔡青利, 汪晓月, 蔡明玉, 等. 干细胞外泌体减轻高糖腹膜透析液诱导的腹膜炎症[J]. 中华肾病研究电子杂志, 2021, 10(5): 252-258. DOI: 10.3877/cma.j.issn.2095-3216.2021.05.003.
CAI Q L, WANG X Y, CAI M Y, et al . Stem cell-derived exosomes alleviated peritonitis induced by high glucose-based peritoneal dialysis dialysate[J ] . Chin J Kidney Dis Investig Electron Ed, 2021, 10(5): 252-258. DOI: 10.3877/cma.j.issn.2095-3216.2021.05.003.
YOKOI H, KASAHARA M, MORI K, et al . Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis[J ] . Kidney Int, 2012, 81(2): 160-169. DOI: 10.1038/ki.2011.305.
NIKFARJAM S, REZAIE J, ZOLBANIN N M, et al . Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine[J ] . J Transl Med, 2020, 18(1): 449. DOI: 10.1186/s12967-020-02622-3.
ZHANG Y, PAN Y J, LIU Y H, et al . Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition[J ] . Stem Cell Res Ther, 2021, 12(1): 434. DOI: 10.1186/s13287-021-02517-0..
WU L, RONG C, ZHOU Q, et al . Bone marrow mesenchymal stem cells ameliorate cisplatin-induced renal fibrosis via miR-146a-5p/Tfdp2 axis in renal tubular epithelial cells[J ] . Front Immunol, 2021, 11: 623693. DOI: 10.3389/fimmu.2020.623693..
HU X M, SHEN N, LIU A Q, et al . Bone marrow mesenchymal stem cell-derived exosomal miR-34c-5p ameliorates RIF by inhibiting the core fucosylation of multiple proteins[J ] . Mol Ther, 2022, 30(2): 763-781. DOI: 10.1016/j.ymthe.2021.10.012.
LI Q M, JIN Y P, YE X Q, et al . Bone marrow mesenchymal stem cell-derived exosomal microRNA-133a restrains myocardial fibrosis and epithelial-mesenchymal transition in viral myocarditis rats through suppressing MAML1[J ] . Nanoscale Res Lett, 2021, 16(1): 111. DOI: 10.1186/s11671-021-03559-2.
KADOTA T, FUJITA Y, ARAYA J, et al . Human bronchial epithelial cell-derived extrace llular vesicle therapy for pulmonary fibrosis via inhibition of TGF-β-WNT crosstalk[J ] . J Extracell Vesicles, 2021, 10(10): e12124. DOI: 10.1002/jev2.12124.
HUANG Y J, CAO J, LEE C Y, et al . Umbilical cord blood plasma-derived exosomes as a novel therapy to reverse liver fibrosis[J ] . Stem Cell Res Ther, 2021, 12(1): 568. DOI: 10.1186/s13287-021-02641-x.
LAI K N, LEUNG J C. Inflammation in peritoneal dialysis[J]. Nephron Clin Pract, 2010, 116(1): c11-c18. DOI: 10.1159/000314544.
MITTELMAIER S, NIWA T, PISCHETSRIEDER M. Chemical and physiological relevance of glucose degradation products in peritoneal dialysis[J]. J Ren Nutr, 2012, 22(1): 181-185. DOI: 10.1053/j.jrn.2011.10.014.
SALZER W L. Peritoneal dialysis-related peritonitis: challenges and solutions[J]. Int J Nephrol Renovasc Dis, 2018, 11: 173-186. DOI: 10.2147/IJNRD.S123618.
HONDA K, HAMADA C, NAKAYAMA M, et al . Impact of uremia, diabetes, and peritoneal dialysis itself on the pathogenesis of peritoneal sclerosis: a quantitative study of peritoneal membrane morphology[J ] . Clin J Am Soc Nephrol, 2008, 3(3): 720-728. DOI: 10. 2215/CJN.03630807.
DEVUYST O, MARGETTS P J, TOPLEY N. The pathophysiology of the peritoneal membrane[J]. J Am Soc Nephrol, 2010, 21(7): 1077-1085. DOI: 10.1681/ASN.2009070694.
ZHOU Q, BAJO M A, DEL PESO G, et al . Preventing peritoneal membrane fibrosis in peritoneal dialysis patients[J ] . Kidney Int, 2016, 90(3): 515-524. DOI: 10.1016/j.kint.2016.03.040.
MUTSAERS S E, PRRÊLE C M, PENGELLY S, et al . Mesothelial cells and peritoneal homeostasis[J ] . Fertil Steril, 2016, 106(5): 1018-1024. DOI: 10.1016/j.fertnstert.2016.09.005.
KASTELEIN A W, VOS L M C, DE JONG K H, et al . Embryology, anatomy, physiology and pathophysiology of the peritoneum and the peritoneal vasculature[J ] . Semin Cell Dev Biol, 2019, 92: 27-36. DOI: 10.1016/j.semcdb.2018.09.007.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621