Dessì S, Batetta B, Pulisci D, Carrucciu A, Mura E, Ferreli A, Pani P
Istituto di Farmacologia e Patologia Biochimica, Università di Cagliari, Italy.
Res Commun Chem Pathol Pharmacol. 1990 Apr;68(1):103-16.
Previous studies by our laboratory have shown that lead nitrate when injected intravenously as a single dose to rats, induces a hyperplastic response in the liver. Liver hyperplasia was accompanied by an increase in cholesterol synthesis, an accumulation of cholesterol esters and by a stimulation of hexose-monophosphate (HMP) shunt enzyme activities. In the present report, hepatic DNA, mitotic index, cholesterol metabolism, as well as glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) activities, were investigated during liver hyperplasia induced by lead in fasted rats. Fasting was chosen as an experimental model characterized by a very strong depression of those metabolic pathways (cholesterol synthesis and HMP shunt) that we have found related to liver hyperplasia. The mitogenic response, even if at minor extent, also occurs in liver of fasted rats. A stimulation of cholesterol synthesis and HMP shunt enzyme activities, was also observed in lead-treated fasted rats, adding further support to the fact that an endogenous source of newly synthesized cholesterol together with a suitable increase of HMP shunt enzyme activities is needed during hepatic cell proliferation.
我们实验室之前的研究表明，当以单剂量静脉注射硝酸铅给大鼠时，会诱导肝脏产生增生反应。肝脏增生伴随着胆固醇合成增加、胆固醇酯积累以及磷酸己糖（HMP）旁路酶活性的刺激。在本报告中，对禁食大鼠在铅诱导的肝脏增生过程中的肝脏DNA、有丝分裂指数、胆固醇代谢以及葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）活性进行了研究。选择禁食作为实验模型，其特征是我们发现与肝脏增生相关的那些代谢途径（胆固醇合成和HMP旁路）受到非常强烈的抑制。有丝分裂反应即使程度较轻，也会在禁食大鼠的肝脏中发生。在铅处理的禁食大鼠中也观察到了胆固醇合成和HMP旁路酶活性的刺激，这进一步支持了在肝细胞增殖过程中需要新合成胆固醇的内源性来源以及HMP旁路酶活性适当增加这一事实。
