胰安肽体外生物稳定性研究及安全性评价

Study on the Stability in Vitro and Safety Evaluation of Aglycin

目的:对生物活性肽胰安肽的体外稳定性进行研究并初步评价其安全性。方法:取胰安肽分别在胃蛋白酶、胰蛋白酶溶液和血浆中进行孵育,采用电泳法和高效液相色谱法考察其酶稳定性和血浆稳定性;对小鼠灌胃给予胰安肽(15 mg.kg-1)38 d,测定脏器(脾、肝、肾和心脏)指数,对胰安肽进行安全性评价;以MTT法研究胰安肽对人肝细胞癌细胞HepG2细胞的体外增殖抑制作用。结果:胰安肽具有抗胃蛋白酶和胰蛋白酶降解作用,在血浆中具有一定的稳定性。连续给药后脏器指数与未给药的空白对照组比较无显著性差异,表明其对各脏器未见损害作用;胰安肽对HepG2细胞未见体外抑制作用。结论:胰安肽体外具有抗胃蛋白酶和胰蛋白酶降解的作用,长期给药安全性较好,具有开发为口服药物的潜力。

OBJECTIVE： To study the stability of bioactive peptide aglycin in vitro,and to evaluate the safety of it.METHODS： Aglycin was incubated in pepsin,trypsase and plasma.The enzymatic and plasma stabilities of aglycin were studied by electrophoresis and HPLC.After intrgastrical administration of aglycin 15 mg·kg-1 for 38 days,the index of spleen,liver,kidney and heart were all determined to evaluate the safety of aglycin.The inhibition effects of aglycin on the proliferation of HepG2 cells in vitro were detected by MTT.RESULTS： Aglycin resisted the degradation effects of pepsin and trypsase,and was stable in plasma.There was no statistically significant difference in organ index between aglycin-treated group and blank control group.Above indicated that aglycin didn＇t affect the organs,and inhibition effect of aglycin on the proliferation of HepG2 cells was not found.CONCLUSION： Aglycin resists the hydrolysis effects of pepsin and trypsase.The safety of drug use is enough as a long-term drug use.It could be developed as potential oral agent.