雷帕霉素免眼房水及血液中药物分布及防治免高危角膜移植后新生血管增殖的研究

目的 探讨雷帕霉素（RAPA）全身和局部使用后兔眼房水及血液中药物含量;观察其对兔眼角膜新生血管增殖的影响.方法 健康新西兰白兔30只,其中20只制作高危角膜移植受体动物模型.将16只兔随机分为4组,每组4只.A组术后不用药,B组涂RAPA眼膏1次/d,C组注射0.5%RAPA豆油注射液2.5mg/kg,2次/d,D组注射0.5 %RAPA豆油注射液1.5mg/kg,2次/d.术后观察90d.用药后1、2、7、14、28、56d高效液相色谱法（HPLC）检测4组兔房水及血液中RAPA 浓度.术后观察术眼新生血管长入情况并记录新生血管指数（NI）,共90d.结果 4组兔各时间点房水及血液中均可检测到RAPA,各组浓度间存在统计学差异.A组术后NI2周后一直呈上升趋势,6周后维持在较高水平;B、C、D组NI一直维持在较低水平.结论 全身或局部用RAPA具有抑制兔眼高危角膜移植后新生血管增殖作用,局部用药优于全身用药.     

Autologous bone marrow-derived mesenchymal stem cells for interstitial fibrosis and tubular atrophy: a pilot study

BackgroundMesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated.MethodsFrom March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson’s trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment.ResultsAt 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-β1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed.ConclusionOur results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-β1: transforming growth factor β1; CTGF: connective tissue growth factor     

慢性同种移植肾病大鼠早期MMP-9的表达

目的探讨基质金属蛋白酶-9(MMP-9)在大鼠慢性同种移植肾病(CAN)早期发病中的表达。方法按照国际标准的慢性同种移植肾病模型要求,以雄性Fisher(F344,RT1V1)大鼠作供体,雄性Lewis(LEW,RT1)为受体进行左肾原位移植。移植后第12周行功能学检查,按照Banff97工作分类标准进行组织学评价以及通过免疫组化检测MMP9和TGFβ1的表达。结果与对照组比较,实验组表现为移植肾肾小球不同程度的系膜增生和局灶节段性硬化,小管间质明显的单个核细胞浸润,局部小管萎缩,小动脉内膜轻度增厚和中层平滑肌细胞增殖并向内膜移行(P<0.01)。MMP-9在早期移植物内的表达增加,并与间质单个核细胞浸润相平行(r=0.77)。结论MMP-9作为一个重要因子参与CAN早期发病并在CAN单个核细胞浸润早期发病事件中起促进作用。