Ogiso T, Kobayashi T, Kato Y
Jpn J Pharmacol. 1975 Aug;25(4):401-9. doi: 10.1254/jjp.25.401.
In order to clarify the action of drugs for liver disease, the effect of protoporphyrin (PP) on CCl4-induced liver injury was studied. Attention was given to the levels of lysosomal enzymes, some components of the liver, and inhibition of enzymes and lysis of lysosomal membranes by lipid peroxides. Administration of PP to CCl4-poisoned rats was found to prevent the decrease in lysosomal lipolytic enzyme level in the liver, but not in other enzyme levels tested. The inhibition of lipolytic enzyme by CCl4 administered may be partially involved in lipid accumulation in the liver. A dose of PP administered to CCl4-poisoned rats for 8 days depressed the neutral lipid content in the liver nearly to the control value. Methyl linoleate hydroperoxide (hydroperoxide) at a lower concentration of 10(-6)% inhibited the lipolytic enzyme acitivity by 30% and in concentrations ranging from 10(-4) to 10(-3)% inhibited beta-glucuronidase activity. Addition of PP to the medium containing 10(-6) to 10(-5)% hydroperoxide and alpha-tocopherol reduced the enzyme inhibition further than in the absence of PP. The hydroperoxide in concentrations varying from 10(-6) to 10(-3)% caused a partial lysis of liver lysosomal membranes, but addition of PP slightly reduced the damage by the hydroperoxide in concentration lower than 10(-5)%.
为了阐明治疗肝病药物的作用，研究了原卟啉（PP）对四氯化碳诱导的肝损伤的影响。重点关注了溶酶体酶水平、肝脏的某些成分，以及脂质过氧化物对酶的抑制作用和溶酶体膜的裂解。给四氯化碳中毒的大鼠施用PP后，发现可防止肝脏中溶酶体脂解酶水平的下降，但对其他所测酶水平无此作用。四氯化碳对脂解酶的抑制作用可能部分参与了肝脏中的脂质蓄积。给四氯化碳中毒的大鼠连续8天施用一定剂量的PP，可使肝脏中的中性脂质含量几乎降至对照值。较低浓度（10^(-6)%）的亚油酸甲酯氢过氧化物（氢过氧化物）可抑制脂解酶活性30%，而浓度在10^(-4)至10^(-3)%范围内时可抑制β-葡萄糖醛酸酶活性。在含有10^(-6)至10^(-5)%氢过氧化物和α-生育酚的培养基中添加PP，比不添加PP时能进一步降低酶的抑制作用。浓度在10^(-6)至10^(-3)%之间变化的氢过氧化物会导致肝溶酶体膜部分裂解，但添加PP可略微减轻浓度低于10^(-5)%的氢过氧化物造成的损伤。
