1.Effect of transplantation of bone marrow mesenchymal stem cells genetically modified with human hepatocyte growth factor gene on angiogenesis in rat lung
Lihua LEI ; Qun LIN ; Caizhu LIN ; Huizhe ZHENG ; Xianzhong LIN ; Fuqiu LIANG ; Hongda CAI ; Qing YANG ; Youguang GAO
Chinese Journal of Anesthesiology 2012;32(4):407-410
Objective To investigate the effect of transplantation of bone marrow mesenchymal stem cells (MSCs) genetically modified with human hepatocyte growth factor gene (hHGF) on angiogenesis in the rat lung.Methods Twenty F344 rats,aged 2 months,weighing 200-250 g,were randomly divided into 2 groups ( n =10 each):HGF group and control group (group C).MSCs genetically modified with hHGF was injected through the external jugular vein in group HGF.While the equal volume of DMEM culture medium (1 ml) was given instead in group C.The mean pulmonary artery pressure was detected at 28 days after transplantation.Then the rats were sacrificed and the lungs were removed for determination of the content of hHGF,expression of proliferating cell nuclear antigen (to reflect the degree of endothelial cell proliferation showed by the small pulmonary vessels) and Ⅷ factor (to reflect the density of the small pulmonary vessels),and microscopic examination.Results Compared with group C,no significant change was found in mean pulmonary artery pressure ( P > 0.05),while the content of hHGF,degree of endothelial cell proliferation,and density of the small pulmonary vessels were significantly increased in group HGF ( P < 0.01).No change was found in the structure of the small pulmonary vessels in group HGF.Conclusion Transplantation of MSCs genetically modified with hHGF can promote angiogenesis in the rat lung.
2.Effect of human hepatocyte growth factor genetic modification on the ameliorating effects of MSCs implantation on pulmonary microvascular rarefaction in a rat model of pulmonary hypertension
Qun LIN ; Lihua LEI ; Caizhu LIN ; Bangxiong ZENG ; Fuqiu LIANG ; Xianzhong LIN ; Huizhe ZHENG ; Hongda CAI ; Youguang GAO ; Qing YANG
Chinese Journal of Anesthesiology 2012;(10):1252-1256
Objective To investigate the effect of human hepatocyte growth factor (hHGF) genetic modification on the ameliorating effects of mesenchymal stem cells (MSCs) implantation on pulmonary microvascular rarefaction in a rat model of pulmonary hypertension (PH).Methods MSCs were obtained from F344 rats and transduced with lentiviral vector modified with human HGF (hHGF-MSCs) or empty vector (EGFP-MSCs).Sixty-six 7 week old male F344 rats weighing 180-250 g were used in this study.PH was induced by left pneumonectomy and subcutaneous monocrotaline (MCT) 60 mg/kg injected at 2 weeks after operation.The animals with PH were randomly divided into 3 groups:control group (group C),EGFP-MSCs group (group E) and HGF-MSCs group (group H).Groups H and E received hHGF-MSCs or EGFP-MSCs 5 × 105 in DMEM 1 ml iv at 3 weeks after subcutaneous MCT injection,while group C received plain DMEM 1 ml.Mean pulmonary arterial pressure (mPAP) was measured and right ventricular hypertrophy and angiogenesis in the lung were assessed and the content of rat HGF (rHGF) and hHGF protein in lung tissue and pulmonary capillary density (by immuno-histochemistry) was measured at 2 weeks after MSCs implantation.The survival rates within 45 days after MCT administration were compared among the 3 groups.Results No hHGF was detected in groups C and E.Both hHGF-MSCs and EGFP-MSCs significantly reduced MPAP and right ventricular hypertrophy and increased pulmonary capillary density and survival rates in groups H and E as compared with group C and the efficacy of hHGF-MSCs was significantly greater than that of EGFP-MSCs.Barium angiography revealed that distal pulmonary vasculature was significantly increased in group H as compared with groups E and C.The survival of the rats receiving hHGF-MSCs was significantly longer in group H than that in groups E and C.Conclusion hHGF genetic modification can improve the ameliorating effects of MSCs implantation on PH-related microvascular rarefaction.
3.Clinical characteristics and risk factors for bilateral pontine infarction:comparison with unilateral pontine infarction
Zhaoxi MA ; Wanhua WANG ; Yan LUO ; Fuqiu GAO ; Yongjun CAO
International Journal of Cerebrovascular Diseases 2019;27(5):325-331
Objective To compare and analyze the etiology,clinical manifestations and imaging differences of bilateral pontine infarction (BPI) and unilateral pontine infarction (UPI),and investigate the possible independent risk factors for BPI.Methods Consecutive patients with pontine infarction admitted to the Department of Neurology,the First People's Hospital of Kunshan from January 2015 to December 2017 were enrolled retrospectively.They were divided into BPI group and UPI group.The risk factors,laboratory findings,National Institutes of Health Stroke Scale (NIHSS) scores,clinical manifestations,and basilar artery lesions were compared between the two groups.Multivariate logistic regression analysis was used to determine the independent risk factors for BPI relative to UPI.Results A total of 131 patients with pontine infarction were enrolled,aged 66.22 ± 12.29 years,97 patients (72.52%) were male;14 (10.69%) were BPI,and 117 (89.31%) were UPI.In terms of clinical symptoms,consciousness disorder (35.71% vs.6.83%;x2 =8.657,P =0.003),quadriplegia (50.00% vs.5.12%;x2 =30.202,P < 0.001),and dysphagia (71.42% vs.29.91%;x2 =7.804,P =0.005) in the BPI group were more common than those in the UPI group.In terms of etiological classification,vertebrobasilar large artery disease (VLAD) was more common in the BPI group (85.71% vs.27.35%;x2 =16.567,P < 0.001),while small artery disease (SAD) was more common in the UPI group (49.57% vs.7.14%;x2 =7.460,P =0.006).In addition,the baseline NIHSS scores (12.43 ±11.1 vs.3.78 ±3.98;t=2.873,P=0.013),white blood cell count ([9.21±2.81] ×109/L vs.[6.92± 2.40] ×109/L;t=3.191,P=0.002),baseline systolic blood pressure (170.57 ±31.21 mmHg vs.156.75 ±23.50 mmHg,1 mmHg =0.133 kPa;t =2.004,P =0.047),as well as the proportion of patients with severe stenosis or occlusion in basilar artery (78.57% vs.8.55%;x2 =40.49,P < 0.001) and with other site infarction (78.57 % vs.11.11%;x2 =33.652,P < 0.001) in the BPI group were significantly higher than those in the UPI group.Multivariate logistic regression analysis showed that severe basilar artery stenosis or occlusion (odds ratio [OR] 20.195,95% confidence interval [CI]2.308-176.703;P =0.007),baseline NIHSS score (OR 1.147,95% CI 1.019-1.292;P =0.023),and infarction at other sites (OR 19.483,95% CI 2.969-127.868;P =0.002) were independently associated with BPI.Conclusion Compared with UPI,patients with BPI had more severe clinical symptoms and most of them with other site infarction.Severe stenosis or occlusion of the basilar artery was an independent risk factor for BPI.