[Effect of mesenchymal stem cells on expression of high mobility group box 1 protein in rats with ischemia reperfusion injury after lung transplantation].

Objective: To establish the ischemia reperfusion injury model in rat after lung transplantation(LT) and explore the expression of high mobility group box 1 protein(HMGB1) after intravenous injection with bone marrow mesenchymal stem cells(MSCs). Methods: Forty healthy 8-10 weeks male SD rats were randomly divided into four groups including the sham-operated group, ischemia-reperfusion (IR), Saline-IR and MSC-IR group. The sham-operated rats were only conducted thoracotomy without lung transplantation and the rest groups were respectively conducted with the left LT, left LT followed by 1 ml saline and left LT followed by 1 ml MSCs (1.0×10(7)/ml). Four groups of rats were killed at 24 h after reperfusion. The blood and left lung tissue were collected. Oxygenation index(OI) and the ratio of wet/dry in four groups were detected and histological sections stained with hematoxylin and eosin (HE) were made. HMGB1 levels in serum were detected with ELISA. Real-time PCR and Western blot were performed to detect the expression of HMGB1 in mRNA and protein levels. Results: The OI in four groups were respectively 383±15, 174±24, 170±30 and 217±21.OI in IR and Saline-IR group decreased compared with the sham-operated group , all P <0.01. The OI increased after injection with MSCs compared with IR group, P <0.01. The histological images showed the marked inflammatory infiltrates and interalveolar septal thickening in IR group. Treatment with MSCs reduced inflammatory injury.The ratio of wet/dry in IR group and Saline-IR group increased compared with the sham-operated group((5.38±0.19), (5.24±0.15) vs (4.16±0.12), all P <0.05). Ratio in MSC-IR group decreased compared with the IR group (4.47±0.14) vs (5.38±0.19), P <0.05. ELISA results showed that HMGB1 level increased significantly in IR group (287±37)ng/ml, Saline-IR group (260±24)ng/ml and MSC-IR group (101±14)ng/ml when compared with the sham-operated group (41±5) ng/ml. The serum HMGB1 level in IR group was positively correlated with the OI ( r =0.759, P <0.05) and wet/dry ratio ( r =0.725, P <0.05). RT-PCR showed that HMGB1 mRNA level in sham-operated group was the lowest and increased significantly in IR group, while decreased significantly in MSC-IR group compared with IR group and Saline-IR group( P <0.01). The results of HMGB1 expression at protein level by Western blot were consistent with the mRNA level. Conclusion: Lung transplantation can induce the expression of HMGB1 but HMGB1 level of lung tissue decreased significantly after the treatment with MSCs, which indicated that MSCs might play an important role in protecting transplanted lung via HMGB1.