Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats
Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats
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DOI：
10.2337/diabetes.54.3.846
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发表时间：
2005-03-01
期刊：
影响因子：
7.7
通讯作者：
Fujikawa, K
中科院分区：
文献类型：
--
作者：
Kato, N;Nemoto, K;Fujikawa, K
周围神经病变是常见的，并最终导致糖尿病的显著发病率。最近，几种神经营养因子已被用于预防糖尿病神经病变的进展。在这项研究中，我们给了重复肌肉注射的人肝细胞生长因子（HGF）基因perhaps，使用脂质体含有血凝病毒的日本（HVJ），检查非病毒基因转移的肝细胞生长因子对实验性糖尿病大鼠感觉运动神经病变的治疗效果。腹腔注射链脲佐菌素引起的实验性糖尿病导致了显着的触觉异常性疼痛（但不是在热痛觉过敏），在减少的传导速度和幅度，并在减少激光多普勒流量的神经和肌肉在6周后的诱导。所有这些变化都被反复的HGF基因转移所逆转。并对神经内膜毛细血管密度及神经形态学变化进行分析。神经内膜毛细血管的密度，披露显着减少糖尿病大鼠，也逆转显着肝细胞生长因子的重复基因转移，然而，没有显着的差异，观察到形态计量在有髓或无髓轴突。这些结果表明，非病毒HVJ脂质体介导的人HGF基因转移有可能安全有效地治疗糖尿病感觉运动神经病变。
Peripheral neuropathy is common and ultimately accounts for significant morbidity in diabetes. Recently, several neurotrophic factors have been used to prevent progression of diabetic neuropathy. In this study, we gave repeated intramuscular injections of the human hepatocyte growth factor (HGF) gene percutaneously, using liposomes containing the hemagglutinating virus of Japan (HVJ), to examine therapeutic efficacy of nonviral gene transfer of HGF for experimental diabetic sensorimotor neuropathy in rats. Experimental diabetes induced by intraperitoneal injection of streptozotocin resulted in a marked tactile allodynia (but not in a thermal hyperalgesia), in a reduction of both the conduction velocity and the amplitude, and in a decreased laser Doppler flux of the nerve and the muscle at 6 weeks after the induction. All these changes were significantly reversed by repeated gene transfer of HGF. Furthermore, we analyzed the density of endoneurial capillaries and morphometrical changes of the nerve. The density of endoneurial capillaries, disclosing marked reduction in diabetic rats, was also reversed significantly by repeated gene transfer of HGF; however, no considerable differences were observed morphometrically in either myelinated or unmyelinated axons. These results suggest that nonviral HVJ liposome-mediated gene transfer of human HGF has potential for the safe effective treatment of diabetic sensorimotor neuropathy.