CAJ | 학술논문

目的观察骨髓间充质干细胞(MSCs)防治大鼠百草枯(PQ)中毒急性肺损伤的作用及可能机制.方法 80只SPF级Wistar大鼠随机(随机数字法)分为4组,每组20只:肺损伤组、MSCs治疗组、MSCs对照组和正常对照组.腹腔注射质量分数为20%的百草枯18 mg/kg制备大鼠中毒模型,正常对照给予磷酸缓冲液(PBS).取第4代MSCs,加入携带增强型绿色荧光蛋白基因的腺病毒载体Ad5-EGFP,转染成功后,在染毒后4 h经尾静脉注射入大鼠体内,分别在给予MSCs后1 d,3 d,7 d,28 d时随机处死每组大鼠各5只,行肺组织病理切片,荧光倒置显微镜观察骨髓间充质干细胞的迁移,于28 d处死各组大鼠取相应标本,检测肺系数、肺匀浆中羟脯氨酸(HYP)的含量、血清转化生长因子-β1(TGF-β1),同时行肺组织病理学观察.结果肺组织病理学观察显示,MSCs治疗组肺纤维化及实变程度较肺损伤组轻,血清转化生长因子-β1(TGF-β1)和肺系数、肺匀浆中经脯氨酸(HYP)的含量均好于损伤组,差异有统计学意义(P均＜0.05).结论 MSCs注入百草枯中毒大鼠体内,通过抑制TGF-β1水平,减少纤维母细胞迁移、活化,抑制胶原蛋白产生,进而保护肺组织结构,可以更有效地抑制肺纤维化、肺实变.
목적 관찰골수간충질간세포(MSCs)방치대서백초고(PQ)중독급성폐손상적작용급가능궤제.방법 80지SPF급Wistar대서수궤(수궤수자법)분위4조,매조20지:폐손상조、MSCs치료조、MSCs대조조화정상대조조.복강주사질량분수위20%적백초고18 mg/kg제비대서중독모형,정상대조급여린산완충액(PBS).취제4대MSCs,가입휴대증강형록색형광단백기인적선병독재체Ad5-EGFP,전염성공후,재염독후4 h경미정맥주사입대서체내,분별재급여MSCs후1 d,3 d,7 d,28 d시수궤처사매조대서각5지,행폐조직병리절편,형광도치현미경관찰골수간충질간세포적천이,우28 d처사각조대서취상응표본,검측폐계수、폐균장중간포안산(HYP)적함량、혈청전화생장인자-β1(TGF-β1),동시행폐조직병이학관찰.결과 폐조직병이학관찰현시,MSCs치료조폐섬유화급실변정도교폐손상조경,혈청전화생장인자-β1(TGF-β1)화폐계수、폐균장중경포안산(HYP)적함량균호우손상조,차이유통계학의의(P균＜0.05).결론 MSCs주입백초고중독대서체내,통과억제TGF-β1수평,감소섬유모세포천이、활화,억제효원단백산생,진이보호폐조직결구,가이경유효지억제폐섬유화、폐실변.
Objective To explore the possible mechanism and protective effect of mesenchymal stem cell (MSC) on rats with paraquat-induced acute lung injury. Method The solution of 20% paraquat (PQ) in dose of 18 mg/kg was injected intra-peritoneally into rats to induce poisoning,and phosphate buffered solution (PBS) was given to rats instead of PQ in rats of control group. Eighty specific pathogen free (SPF) Wistar rats were randomly divided into four group: PQ plus PBS group (n = 20), PQ plus MSCs group (n = 20), MSCs plus PBS group (n=20), normal group (n = 20). The forth generation of MSCs were transfected with Ad5-EGFP virus vector, and then the MSCs-EGFP was delivered to rats through the tail vein of rats 4h after PQ. Five rats of each group were sacrificed 1 d, 3 d, 7 d and 28 days after MSCs administration, and lung tissues of rats were taken to make sections for histological observation of the migration of MSCs under fluorescence inverted microscope. The lung tissues of rats sacrificed on the 28 th day after PQ poisoning were taken for detecting pulmonary coefficient and the content of hydroxyproline (HYP) in the lung tissue homogenate, and at the same time, the levels of serum transforming growth factor-β1(TGF-β1) were assayed. Results The pathological changes of lung tissue showed that the pulmonary fibrosis and consolidation in the MSCs treatment group were milder than those in PQ poisoning model group. In the MSCs treatment group, the levels of serum TGF-β1 and lung tissue HYP, and pulmonary coefficient were lower than those of PQ poisoning model group (P＜0.05). Conclusions The use of MSCs for treatment of paraquat intoxication can protect pulmonary structure by decrease in TGF-B1 and inhibiting the fibroblast migration, suppressing the production of collagenous protein.