锌二氢卟吩f的合成及其对急性肝损伤的保护作用和抗溃疡活性

Synthesis of zinc chlorin f and its experimental antigastric ulcer activity and protective effect on acute liver injury

目的 :研究锌二氢卟吩 f (3)的合成及实验性抗溃疡活性和对急性肝损伤的保护作用。 方法 :蚕沙叶绿素粗品经酸碱降解反应制得二氢卟吩 f (2 ) ,(2 )与醋酸锌络合制得锌二氢卟吩 f (3)。通过给大鼠 ip 0 .2 %吲哚美辛 (2 0 m g/ kg)制备胃溃疡模型 ,测定溃疡指数和溃疡个数 ;以 0 .3%硫代乙酰胺 (30 mg/ kg)和 0 .3%四氯化碳 (30 m g/ kg)分别 ip小鼠形成急性肝损伤 ,测定血清 AL T活性。观察 ip化合物 (3)后对急性肝损伤的保护作用和抗溃疡活性。 结果 :锌二氢卟吩 f (3)为新化合物。ip化合物 (3) 80 m g/ kg,能显著降低吲哚美辛诱发的大鼠胃溃疡指数 (P<0 .0 0 1)和溃疡个数 (P<0 .0 0 1)。 ip化合物 (3) 10 0mg/ kg× 3,能显著降低小鼠硫代乙酰胺 (P<0 .0 1)和四氯化碳 (P<0 .0 5 )急性肝损伤后升高的 AL T活性。 结论 :化合物 (3)对吲哚美辛诱发的大鼠胃溃疡和硫代乙酰胺、四氯化碳所致小鼠急性肝损伤具有显著的保护作用 ,提示化合物 (3)是一种有开发前景的抗溃疡和保肝侯选化合物 。

Objective: To synthesize zinc chlorin f (3) and to study its experimental antigastric ulcer activity and its protective effects on acute liver injuries. Methods: Compound (3) was synthesized via Zn(OAc) 2 complex reaction with chlorin f (2), which was prepared through acidic and alkaline oxidative degradation with silkworm excrement crude chlorophyll extracts as starting material.Gastric ulcers were induced by abdominal injection of 0.2% indomethacin at 20 mg/kg in rats. The ulcer indexes and ulcer numbers in gastric mucosa were determined. Acute liver injuries were induced by abdominal injection of 0.3% thioacetamide(TAA) or 0.3% CCl 4 at 30 mg/kg in mice,and activities of ALT in mice were determined. Results: Zinc chlorinf (3) was a new compound. Compared with control group,abdominal administration of (3) at 80 mg/kg significantly reduced the gastric ulcer index( P <0.001) and the number of ulcer( P <0.001) induced by indomethacin in rats,and abdominal administration of (3) at 100 mg/kg×3 exhibited markedly inhibitory effects on elevated activities of ALT induced by TAA( P <0.01) or CCl 4( P <0.05) in mice. Conclusion: Compound (3) has significant protective effect against indomethacin induced gastric lesion in rats and TAA or CCl 4 induced acute liver injuries in mice.It is suggested that compound (3) may be a promising new antigastric ulcer and liver injury protective drug.