CAJ | 학술논문

目的：探讨Ad-HIF-1α-Trip 基因转染兔缺血后肢的部分安全性。方法：22只新西兰大白兔建立急性左后肢缺血模型，随机分为生理盐水组（Saline 组，n＝6）、腺病毒空载体组（Ad-Null组，n＝6）、Ad-HIF-1α-Trip组（n＝10）。分别在术后即刻肌注生理盐水、Ad-Null、Ad-HIF-1α-Trip 。术后10 d Ad-HIF-1α-Trip组取4只行Real-time PCR了解HIF-1α-Trip转染后在缺血后肢及在心、肝、肾、肺的表达情况；术前、术后3 d、7 d、14 d、28 d ，测量体温、体重，检测肝及肾功能、心肌酶；术后28 d 对Ad-HIF-1α-Trip 组心、肝、肾、肺进行HE染色，了解有无严重病理改变。结果：转染后10 d，Ad-HIF-1α-Trip 组缺血骨骼肌HIF-1α-Trip 转染后有确切表达；心、肝、肾、肺未见表达。3组实验兔血常规、肝肾功能指标均在正常值范围，组间对比差异无统计学意义（P＞0．05）。 Ad-HIF-1α-Trip组心、肝、肾、肺HE染色未见明显异常。结论：Ad-HIF-1α-Trip单次肌肉注射能在兔缺血后肢明确表达，且未发现明显毒副反应。
목적：탐토Ad-HIF-1α-Trip 기인전염토결혈후지적부분안전성。방법：22지신서란대백토건립급성좌후지결혈모형，수궤분위생리염수조（Saline 조，n＝6）、선병독공재체조（Ad-Null조，n＝6）、Ad-HIF-1α-Trip조（n＝10）。분별재술후즉각기주생리염수、Ad-Null、Ad-HIF-1α-Trip 。술후10 d Ad-HIF-1α-Trip조취4지행Real-time PCR료해HIF-1α-Trip전염후재결혈후지급재심、간、신、폐적표체정황；술전、술후3 d、7 d、14 d、28 d ，측량체온、체중，검측간급신공능、심기매；술후28 d 대Ad-HIF-1α-Trip 조심、간、신、폐진행HE염색，료해유무엄중병리개변。결과：전염후10 d，Ad-HIF-1α-Trip 조결혈골격기HIF-1α-Trip 전염후유학절표체；심、간、신、폐미견표체。3조실험토혈상규、간신공능지표균재정상치범위，조간대비차이무통계학의의（P＞0．05）。 Ad-HIF-1α-Trip조심、간、신、폐HE염색미견명현이상。결론：Ad-HIF-1α-Trip단차기육주사능재토결혈후지명학표체，차미발현명현독부반응。
Objective To investigate the partial safety of the recombinant adenovirus containing the triple-point mutants HIF-1αgene (Ad-HIF-1α-Trip)transfection in a rabbit model of hind limb ischemia. Methods After ligation of left femoral artery, 22 New Zealand whites rabbits were randomly divided into 3 groups: saline group(n=6), Ad-Null group(n=6) and Ad-HIF-1α-Trip group(n=10). After operation, saline, Ad-Null and Ad-HIF-1αwere injected intramuscularly respectively. The expression of transferred HIF-1αat mRNA level in the ischemic skeletal muscle and other important organs were detected by Real-time PCR 10 days after gene transfection. The body temperature, weight, blood, liver and renal function, as well as the myocardial enzymes were detected before operation, and on the 3th, 7th, 14th and 28th day after gene transfection, so that pathological changes could be observed. Results On the 10th day after gene transfection, obvious expressions of HIF-1αat mRNA level in the ischemic limb were found, but no expression in other important organs was detected in Ad-HIF-1α-Trip group. The blood routine, liver and renal function were all in the normal range (P > 0.05). No abnormalities were found in heart, liver, kidney, and lung HE transfection in Ad-HIF-1α-Trip group. Conclusion Single intramuscular injection of Ad-HIF-1α-Trip can be expressed obviously in the ischemic limb without detected damage of liver , cardiac and kidney.