1.Protective effect of ginkgo biloba extract on pancreas transplantation in type 2 diabetic rats
Xiaonan LIU ; Tingting HUG ; Weizhong WANG ; Guanglong DONG ; Hongwei ZHANG ; Dongli CHEN
Chinese Journal of Tissue Engineering Research 2006;10(27):175-177
BACKGROUND: Ginkgo biloba extract (GBE) has the pharmacological actions of antioxidation, eliminating free radicals and anti-platelet activating factors, it also can relieve the ischemia/reperfusion injury of various organs.OBJECTIVE: Toobserve whether GBE can relieve the ischemia/reperfusion injury of transplanted pancreas in diabetic rats or not.DESIGN: A complete randomized grouping design, controlled study.SETTINGS: Department of Gastrointestinal Surgery and Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University of Chinese PLA Hospital.MATERIALS: Totally 128 male SD rats of clean grade, aged 3-6 months,weighing 250-320 g, were used. GBE was produced by Dr. Willmar Schwabe Pharmaceuti - cals (Ginaton parenteral solution, 5 mL/piece, containing 17.5 mg GBE, including 4.2 mg ginkgo flavone glycosides, batch number: 1511102).METHODS: The experiments were carried out in the laboratory of Department of Gastrointestinal Surgery from September 2001 to April 2004.① Eighty rats were injected with STZ (65 mg/kg) via penile vein, and 60 of them with fasting blood glucose exceeding 17.4 mmol/L for 2weeks were taken as the diabetic rats, and the other 48 normal rats were taken as donors. ② The 60 diabetic rats were randomly divided into two groups: ischemia/reperfusion group (n=30) and GBE group (n=30), and pancreas transplantation was performed in both groups. In the ischemia/reperfusion group, the rats were douched with 4 ℃ iced balanced salt solution containing heparin (1.5×105 U/L) for 20 minutes. In the GBE group, the recipients were given intravenous injection of GBE (1.5 mL/kg) at 1 day and 30 minutes before transplantation, and those in the ischemia/reperfusion group were intravenously injected with saline of the same volume. The donor pancreases were all reserved in 4 ℃ iced balanced salt solution containing heparin (1.5×105 U/L), the cold and hot ischemia times were kept for 180 and 15 minutes in each group to induce ischemia/reperfusion injury of transplanted pancreas. ③ Six randomly selected rats were killed at 2 days before transplantation and at 3 and 7days after transplantation respectively to detect fasting blood glucose; The activity of amylase was determined with corresponding kit provided by Nanjing Jiancheng Bioengineering Institute; Pancreas tissues were removed for hematoxylin and eosin (HE) staining; Six rats were used to observe the metabolic indexes; The other 6 rats were used to observe the survival rate within 1 month. ④ The differences of the measurement data were compared with the paired t test.MAIN OUTCOME MEASURES: ① Changes of fasting blood glucose level, metabolic indexes and activity of amylase before and after pancreas transplantation in the rat recipients of both groups; ② Pathological changes at 3 and 7 days after transplantation in the rat recipients of both groups.RESULTS: All the 60 rat as recipients finished the detections of blood glucose, food intake, water intake, urinary output and blood amylase. ①The survival rate within 1 month after transplantation was obviously higher in the GBE group than in the ischemia/reperfusion group (83%, 33%, P< 0.01). ② The blood glucose, water intake, food intake and the urinary output at 3 and 7 days after transplantation were obviously decreased as compared with those at 2 days before transplantation in both theischemia/reperfusion group and GBE group (P < 0.05-0.01), and those at 3 and 7days after transplantation were obviously lower in the GBE group than in the ischemia/reperfusion group (P < 0.05-0.01). ③ The activity of blood amylase at 3 days after transplantation was obviously increased as compared with that before transplantation in both the ischemia/reperfusion group and the GBE group (P < 0.01, 0.05), it was still obviously higher at 7 days after transplantation than at 2 days before transplantation in the ischemia/reperfusion group (P < 0.01), and it had almost recovered to normal in the GBE group. The activities of blood amylase at 3 and 7 days after transplantation were obviously lower in the GBE group than in the ischemia/reperfusion group (P < 0.01). ④ The results of the pathological observation showed that the damaged severity of the transplanted pancreas was greater in the ischemia/reperfusion group than in the GEB group.CONCLUSION: GBE pretreatment can improve the survival rate of pancreas transplantation in rats, reduce the activity of blood amylase, ameliorate the metabolism, relieve the severity of reperfusion injury of pancreas,and plays a protective role in the pancreas transplantation.