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目的:观察汉防己甲素(tetrandrine,Tet)对大鼠实验性急性胰腺炎(acute pancreatitis,AP)的治疗效果,并探讨其作用机制。方法:取176只 SD 大鼠,雌雄不拘,随机分为假手术组、Tet 低、中、高剂量组、异搏定组及生理盐水组,经胰胆管逆行注射3%牛磺脱氧胆酸钠0.1 ml/100g 体重,制成急性胰腺炎模型,记录4 h、8 h 腹水量;测定血浆中钙离子浓度和淀粉酶活性、胰腺组织匀浆及腹水中磷脂酶 A_2(PLA_2)活性的变化。光镜下观察胰组织的变化;记录动物的存活时间及24 h 死亡率。结果:Tet 能有效减轻 AP 大鼠胰腺的病理性损伤;减少腹水生成;与生理盐水组相比,Tet 组血浆中钙离子浓度进行性下降的程度减轻,淀粉酶活性降低、腹水中 PLA_2活性显著降低;Tet 可降低 AP 大鼠的死亡率,延长动物的生存时间。结论:汉防己甲素可以通过钙通道拮抗作用、抑制 PLA_2的活性,减轻胰腺腺泡细胞的损伤而对急性胰腺炎发挥保护作用。
Objective: To observe the therapeutic effect of tetrandrine (Tet) on experimental acute pancreatitis (AP) in rats and to explore its mechanism of action. METHODS: A total of 176 SD rats, either male or female, were randomly divided into sham-operated group, low-, medium-, high-dose Tet, verapamil, and saline groups. 3% tauro-sodium deoxycholate was injected retrograde through the pancreatic ducts. 0.1 ml/100 g body weight was made into acute pancreatitis model, and the amount of ascites was recorded at 4 and 8 hours. Plasma calcium ion concentration, amylase activity, pancreatic homogenate and ascitic fluid phospholipase A 2 (PLA 2) activity were measured. The change of pancreatic tissue was observed under light microscope; the animal’s survival time and 24 h mortality rate were recorded. RESULTS: Tet could effectively reduce the pathological damage of pancreas in AP rats and reduce the production of ascites. Compared with saline group, the degree of the decrease of plasma calcium concentration in the Tet group decreased, the activity of amylase decreased, and the activity of PLA-2 in ascites was significant. Decrease; Tet can reduce the mortality rate of AP rats and prolong the survival time of animals. Conclusion: Tetrandrine can protect against acute pancreatitis by antagonizing calcium channels, inhibiting the activity of PLA_2, and reducing the damage of pancreatic acinar cells.