| Objective:. 1. To investigate the effects of recombinant human basic fibroblastgrowth factor (rh-bFGF) combined with salvia miltiorrhiza in treating ischemichindlimb of the rabbit model. 2.To evaluate the safety of rh-bFGF combined withsalvia miltiorrhiza, and the effect of salvia miltiorrhiza in relieving the side effects ofrh-bFGF by testing the blood, liver and kidney function, digital subtraction andpathologic observation.Material and methods: 40 rabbits were used to establish the animal modelof lower limb ischemia by removing the left femoral artery and ligating its branchvessels. Group A, B, C, D were injected with 10μg bFGF, 2ml/kg salvia miltiorrhiza,10μg bFGF combined with 2ml/kg salvia miltiorrhiza, and normal saline respectivelyat 10th day after establishing the model. All rabbits were put to death at 30th days afteroperation. The blood pressure and angiography were observed after treatment. Theblood and tissue samples were analyzed for the physiological function andangiogenesis of the rabbits.Results: 1. Clinical observation: Rabbits of each group were all alive in theperiod of experiment, and showed some kinds of hindlimb ischemic symptoms afteroperation, such as: claudication, lipsotrichia, redness, defluviam, and so on. Group Dwere observed that the ischemic syrnptoms still existed in the end. One rabbit ingroup D(10%) got ischemic ulcer of digitipedis, and symptoms became severe in thisgroup. However, group A, B, C had no anabrosis of digitipedis, their tresis vulnus healing well, and symptoms got relieved after drug administraton.2. The calf blood pressure ratio: The calf blood pressure could not be detected in10th days after model was made. At the end of treatment, significant improvements incollateral formation and hind limb perfusion were observed in group A, B, Ccompared with the control group (calf blood pressure ratio: 0.64±0.028,0.50±0.031,0.80±0.022,0.28±0.032, respectively). There is significant statistical differenceamong group C with group A and B, and between group A and B. The outcome ofgroup C is the best.3. Digital subtraction angiography: Femoral artery and its branches vessels couldnot be found in the operated limb. There is minor angiogenesis in group D, only a fewsmall vessels in the mid thigh. But, there are prominent collateral circulationestablished in the experimental groups, especially in group C. These vessels creep inmid thigh and distribute reticulodromously; and internal iliac artery and femoral arteryof the operated hindlimb became pachy because of compensation. There are novascular malformation and normal vessels becoming narrowed in the treatment groupA and C.4. Microvessel density and microvessel density/ muscle fiber ratio: There issignificant difference between treatment groups and control group (P＜0.01),especially in group C.5. Pathological results: Rabbits in the control group exhibited severe ischernicchanges. There were few small vessels between skeletal muscles and no hyperplasticendothelium and the skeletal muscle were ischemic and denaturalizated in group D.But there are prominent angiogenesis and collateral circulation formation in group A,B, C. The ischemic symptom of the experimental groups were catabatic. There are nomalformed capillaries and tumorous vessels in treatment groups.6. Blood Routine Examination: The blood samples were analyzed for thehemogram at the day before the operation and 20th and 30th day after the procedure.All the results in 4 groups were in normal references. There is no statistical difference among each groups.7. Liver and kidney function: The blood samples were analyzed for ALT, AST,BUN and Cr at 20th and 30th day after the procedure. All the results were in normalreferences. There is no statistical difference among each groups.Conclusion: 1. Combined intramuscular administration of bFGF and salviamiltiorrhiza in multiple spots in short-term induced therapeutic angiogenesis andcollateral circulation formation in the rabbit models of chronic hind limb ischemia.Thus, the combined administration may be a new therapeutic strategy for thetreatment of peripheral vascular diseases, especially diabetes hind limb ischemia. 2. Asingle administration of bFGF can induce ectopic vascular stricture. 3. Salviamiltiorrhiza has a synergic effect and can relieve the side effects of bFGF. |
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