Nakae Mika, Kamiya Hideki, Naruse Keiko, Horio Naoichi, Ito Yasuki, Mizubayashi Ryuichi, Hamada Yoji, Nakashima Eitaro, Akiyama Noboru, Kobayashi Yasuko, Watarai Atsuko, Kimura Nachi, Horiguchi Masayuki, Tabata Yasuhiko, Oiso Yutaka, Nakamura Jiro
Division of Metabolic Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Diabetes. 2006 May;55(5):1470-7. doi: 10.2337/db05-1160.
Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetic rats were treated with human recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH), and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves, hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by intravenous administration of bFGF after 10, but not 30, days. Intramuscular injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and SNBF after 10 and 30 days, but caudal MNCV was not improved. However, intramuscular injection of bFGF with saline had no significant effects. bFGF did not significantly alter RBF in either normal or diabetic rats. These observations suggest that bFGF could have therapeutic value for diabetic neuropathy and that CGH could play important roles as a carrier of bFGF.
碱性成纤维细胞生长因子(bFGF)可刺激血管生成并诱导神经细胞再生。我们研究了bFGF对链脲佐菌素诱导的糖尿病大鼠糖尿病神经病变的影响。糖尿病大鼠接受人重组bFGF治疗如下:1)静脉给药;2)用交联明胶水凝胶(CGH)肌肉注射到大腿和比目鱼肌;3)用生理盐水肌肉注射。10天或30天后,测量坐骨-胫神经和尾神经的运动神经传导速度(MNCV)、对机械刺激的敏感性、坐骨神经血流量(SNBF)和视网膜血流量(RBF)。糖尿病大鼠坐骨-胫神经和尾神经的MNCV延迟、痛觉减退和SNBF降低,在10天后通过静脉注射bFGF均得到改善,但30天后未改善。10天和30天后,用CGH肌肉注射bFGF也改善了坐骨-胫神经MNCV、痛觉减退和SNBF,但尾神经MNCV未改善。然而,用生理盐水肌肉注射bFGF没有显著效果。bFGF对正常或糖尿病大鼠的RBF均无显著影响。这些观察结果表明,bFGF对糖尿病神经病变可能具有治疗价值,并且CGH作为bFGF的载体可能发挥重要作用。