| Objective: In order to explore the possibility of xenotransplantation to solve the shortage of organ origin.This experiment design to evaluate the expression of heme oxygenase-1(HO-1) in xenograft of mouse to rat cardiac transplantation and to study the effect of HO-1 on delay xenograft mouse to rat cardiac transplantation, which was induced by means of heat shock preconditioning and cobalt protoporphyrin, Methods and Results Part 1,The anesthesia method in modal of ectopia xenocardiac mouse(NIH) to rat(Wistar) with cuff was modified from once intraperitoneal injection to half dosage at first time and then increased it step by step, and the pulmonary veins of donor was deal with independently. The successful rate of operation were 80 percent(16/20) and 90 percent(18/20) respectively, mean survival time of xenograft was 2.10 土0.7379day, mean blooding was 0.82±0.24ml and 0.32±0.17ml between improved or not(t=2.6321,P<0.01), the operating time before improved was 115.25±30.20minutes and after that was 86.31±14.56minutes(t= 3.8603,P﹤0.001). No differences were found between IgA, IgG, IgM, C3 and C4 in serum of control group and that in transplanted group serum(t=0.5460 ,P>0.05)。The rejected heart was swelled and the histology of the rejected showed widespread intravascular thrombosis, hemorrhage, associated with a large number of infiltrated inf1ammatory cel1s, foca1 ischemic infarcts and coagulate necrosis. Immunohistochemistry showed no C3 were deposited in the xenograft, however 70.59%(24/34) xenograft had IgG deposition. Immunostaining for CD68 found macrophage were the major cells of the infiltrated inf1ammatory cells. So this model can be used to study DXR and the improved strategy could reduced blood and shorten the operating time. Part 2. The HO-1 protein and HO-1mRNA in mouse to rat cardiac xenograft were assessed by means of immunohistochemistry, reverse-transcriptase polymerase chain reaction as well as Western Blot and the HO-1 activity was assayed too. The HO-1 located at vascular endothelial cell and myocardial cell, which close to vascular, at the same time, HO-1 expressed in infiltrated inf1ammatory cells. The HO-1mRNA increased at 6 hour after transplantation(0.03209±0.012051) and reached summit 24 hour later (0.16752±0.0304496),began to descend at 48 hour(0.150875±0.027486). The summit of HO-1 protein was 48 hour and it concord with HO-1 enzymatic activity. The result revealed that HO-1 protein expression and enzymatic activity summit was delayed fromHO-1mRNA, even all summit of them were between 24 to 48 hour, and they were began to descend at the time of rejection take place. The concord cardiac xenotranplantation, in which the rejection occurred at 2-3 day later, was suited to study the effect of HO-1 on it. Part 3.This study was designed to investigate the preconditioning, heat shock, induced HO-1 in NIH mouse and the effect of HO-1 on DXR in the model of mouse to rat cardiac transplantation. The heater was used to heat NIH mouse, the temperature of mouse was maintain at 42 ℃ at least 20 minutes during heat shock preconditioning. The liver, spleen and heart of mouse were harvested 1h, 6h, 12h, 24h, 48h and 72h after heat shock respectively. The HO-1 was assayed by means of immunohistochemistry, reverse-transcriptase polymerase chain reaction as well as Westrn Blot and the HO-1 activity was assayed too. The heart, harvested from preconditioning mouse, was transplanted in follow group: A, control group(n=8);B,heat shock group(n=8);C,heat shock and zinc protoporphyrin(ZnPP) group 1.5mg/kgd(n=8); D,heat shock and cobalt protoporphyrin(CoPP) 5mg/Kgd group (n=8 ) ; E heat shock group combined zinc ZnPP and CoPP(n=8)。The results showed that HO-1 was induced in liver, spleen and heart of mouse, the summit of HO-1 protein in cardiac was 24 hour later and it began to descend at the time of 48 hour. The survival time of transplanted heart in heat shock group(4.750±1.3628) was significantly longer than that in control group(t=5.70252,P<0.001)and heat shock combined ZnPP group(t=4.91295...
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