重组人胰岛素原基因质粒在糖尿病鼠体内表达的安全性初步研究

Study on Safety of Expression of Recombinant Human Proinsulin Gene Plasmid in Diabetic Rats

目的初步研究重组人胰岛素原基因逆转录病毒载体质粒(RHPGP)在糖尿病大鼠体内的安全性。方法将三碘甲腺原氨酸(T3)和肝细胞生长因子(HGF)注射入糖尿病鼠体内后,导入RHIGP,检测血糖、血清谷丙转氨酶(ALT)、白蛋白(ALB)、肌酐(CRE)和尿素氮(BUN),进行24h饥饿试验以及组织病理学检测和逆转录病毒复制完整型病毒(RCR)的检测。结果实验组大鼠血糖明显下降,饥饿试验中未有低血糖事件发生;实验组动物的ALT、ALB、CRE和BUN与正常组大鼠无统计学差异;病理检测光镜下未见癌细胞及异形核细胞;未检测到野生型逆转录病毒。结论我们构建RHIGP体内表达实现了安全性调控;RHIGP应用于活体动物是安全的。

Objective To study primarily the safety of transfering recombinant human proinsulin gene plasmid （RHPGP） into diabetic rats induced by streptozotocin. Methods After the injection of triiodothyronine （T3） and hepatocyte growth factor （HGF） to the diabetic rats, RHPGP was transferred. 24-hours fasting test was conducted and the alanine aminotransferase （ALT）,albumin （ALB）,creatinine （CRE） and blood urea nitrogen （BUN） were detected as well as the examination of blood glucose. Then some kind of tissues were gathered for histopathological detection and for PCR to determine the presence of the replication-competent retrovirus（RCR）. Results Blood glucose decreased obviously and there was no hypoglycemia in the 24-hours fasting test. The values of ALT, ALB, CRE, and BUN of the experimental rats were not different from those of the rats of normal control （P 〉 0.05 ）. No tumor or malignant cells were seen in the rats of the experiment group. There was no replication-competent retrovirus detected. Conclusion The expression of RHPGP implements safe regulation and RHPGP can be safely used to rats.