BACKGROUND： Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new...BACKGROUND： Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new vessels and form collateral circulation. OBJECTIVE： To observe histopathological changes in the femoral and intramuscular nerve three months after intramuscular injection of hepatocyte growth factor （HGF） into the peripheral skeletal muscle in a canine model of lower limb ischemia. DESIGN： Randomized occlusion modelled and verification animal study. SETTING： Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA. MATERIALS： This study was performed at Animal Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from September to November 2006. A total of eight male mongrel dogs, weighing 12–15 kg and 1.5–3 years of age, were selected for this study. This experimental study was in accordance with local ethics standards. Recombinant plasmid carrying HGF （pUDKH） and occlusion model plasmid （pUDK） were provided by the Third Laboratory of Radiation Medical Institute, Academy of Military Medical Sciences of PLA. METHODS： Grouping and model establishment： under anesthesia, complete vascular occlusion models were established on the left lower extremities. The experimental dogs were randomly divided into a model group and a pUDKH treatment group, with four dogs in each group. Dogs in the pUDKH group were injected with 0.15 mg/kg pUDKH. Ten minutes later, intramuscular injections were performed at three spots into the peripheral skeletal muscle of the left hind limb, as well as lateral injections at two spots. The injection volume at each spot was 0.2 mL. Dogs in the model group were injected with pUDK, and dosage and injection method were identical to the treatment group. MAIN OUTCOME MEASURES： Histopathological changes in the femoral nerve, as well as internal and external intramuscular nerve tissues in the hind limb of dogs three months after plasmid injection under optic microscope. RESULTS： （1） Histopathological changes in the femoral nerve： tiny nerves from the femoral nerve to the intramuscular nerve exhibited marked degeneration in the model group. The degenerating features included neurites, myelin sheaths, and Schwann cell nuclei. Neuropathy in the pUDKH treatment group was not detected. （2） Histopathological changes of the intramuscular nerve： large and irregular vacuoles were present on several longitudinal sections of intramuscular nerve fibers in the model group, as well as annular-shaped blank regions on transverse sections of peripheral neurites. In the pUDKH treatment group, large, blank regions were present in several segments of partial nerve fibers of the longitudinal intramuscular nerve region, but only a few nerve fibers exhibited annular-shaped blank regions on the transverse section of peripheral neurites. CONCLUSION： Local pUDKH injection may relieve or block femoral and intramuscular nerve tissue injury in a canine mocel of lower limb ischemia.展开更多
目的探讨碱性成纤维细胞生长因子(bFGF)联合肝素治疗下肢慢性缺血的作用。材料与方法采用切除左侧后肢股动脉方法制作兔下肢慢性缺血模型。18只兔随机分为3组,A组为对照组,B、C为治疗组,分别经肌肉注射bFGF 10μg+5ml mM Tris缓冲液、bF...目的探讨碱性成纤维细胞生长因子(bFGF)联合肝素治疗下肢慢性缺血的作用。材料与方法采用切除左侧后肢股动脉方法制作兔下肢慢性缺血模型。18只兔随机分为3组,A组为对照组,B、C为治疗组,分别经肌肉注射bFGF 10μg+5ml mM Tris缓冲液、bFGF 10μg+5ml mM Tris缓冲液+肝素1000 U。处死前行血管造影、毛细血管密度检测及病理学检查。结果治疗组血压显著高于对照组,C组高于B组。治疗组可见丰富的侧支血管形成,微血管密度和微血管/肌纤维束比值较对照组明显增高;C组明显高于B组。结论肌肉注射bFGF能有效促进缺血肢体血管新生,是治疗下肢远端缺血性病变有效方法之一。肝素对bFGF具有协同促进作用,可显著增强其生物效应。展开更多
基金the Foundation of High-Tech Key Project of the National 863 Program, No. 2001AA217061
文摘BACKGROUND： Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new vessels and form collateral circulation. OBJECTIVE： To observe histopathological changes in the femoral and intramuscular nerve three months after intramuscular injection of hepatocyte growth factor （HGF） into the peripheral skeletal muscle in a canine model of lower limb ischemia. DESIGN： Randomized occlusion modelled and verification animal study. SETTING： Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA. MATERIALS： This study was performed at Animal Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from September to November 2006. A total of eight male mongrel dogs, weighing 12–15 kg and 1.5–3 years of age, were selected for this study. This experimental study was in accordance with local ethics standards. Recombinant plasmid carrying HGF （pUDKH） and occlusion model plasmid （pUDK） were provided by the Third Laboratory of Radiation Medical Institute, Academy of Military Medical Sciences of PLA. METHODS： Grouping and model establishment： under anesthesia, complete vascular occlusion models were established on the left lower extremities. The experimental dogs were randomly divided into a model group and a pUDKH treatment group, with four dogs in each group. Dogs in the pUDKH group were injected with 0.15 mg/kg pUDKH. Ten minutes later, intramuscular injections were performed at three spots into the peripheral skeletal muscle of the left hind limb, as well as lateral injections at two spots. The injection volume at each spot was 0.2 mL. Dogs in the model group were injected with pUDK, and dosage and injection method were identical to the treatment group. MAIN OUTCOME MEASURES： Histopathological changes in the femoral nerve, as well as internal and external intramuscular nerve tissues in the hind limb of dogs three months after plasmid injection under optic microscope. RESULTS： （1） Histopathological changes in the femoral nerve： tiny nerves from the femoral nerve to the intramuscular nerve exhibited marked degeneration in the model group. The degenerating features included neurites, myelin sheaths, and Schwann cell nuclei. Neuropathy in the pUDKH treatment group was not detected. （2） Histopathological changes of the intramuscular nerve： large and irregular vacuoles were present on several longitudinal sections of intramuscular nerve fibers in the model group, as well as annular-shaped blank regions on transverse sections of peripheral neurites. In the pUDKH treatment group, large, blank regions were present in several segments of partial nerve fibers of the longitudinal intramuscular nerve region, but only a few nerve fibers exhibited annular-shaped blank regions on the transverse section of peripheral neurites. CONCLUSION： Local pUDKH injection may relieve or block femoral and intramuscular nerve tissue injury in a canine mocel of lower limb ischemia.
文摘目的探讨碱性成纤维细胞生长因子(bFGF)联合肝素治疗下肢慢性缺血的作用。材料与方法采用切除左侧后肢股动脉方法制作兔下肢慢性缺血模型。18只兔随机分为3组,A组为对照组,B、C为治疗组,分别经肌肉注射bFGF 10μg+5ml mM Tris缓冲液、bFGF 10μg+5ml mM Tris缓冲液+肝素1000 U。处死前行血管造影、毛细血管密度检测及病理学检查。结果治疗组血压显著高于对照组,C组高于B组。治疗组可见丰富的侧支血管形成,微血管密度和微血管/肌纤维束比值较对照组明显增高;C组明显高于B组。结论肌肉注射bFGF能有效促进缺血肢体血管新生,是治疗下肢远端缺血性病变有效方法之一。肝素对bFGF具有协同促进作用,可显著增强其生物效应。
