Srinivasan S R, Chow C K, Glauert H P
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506.
Toxicology. 1990 Jun;62(3):321-32. doi: 10.1016/0300-483x(90)90055-l.
The peroxisome proliferator ciprofibrate was examined for its ability to alter liver regrowth following partial hepatectomy in rats. Ciprofibrate was fed to female Sprague-Dawley rats at concentrations of 0, 0.01% and 0.025% in the diet for 2 weeks. All rats were then subjected to partial hepatectomy and were killed at 0, 12, 24, 36, 48, 72, and 168 h afterwards. The increase in liver weight after partial hepatectomy occurred at a similar rate in control and ciprofibrate-fed rats, although liver weights were always higher in ciprofibrate-fed rats. The marked increase in DNA synthesis normally seen after partial hepatectomy, however, was partially inhibited in rats fed 0.025% ciprofibrate, as compared to control rats or rats fed 0.01% ciprofibrate. An increase in the ratio of protein to DNA in the liver was observed in rats fed either level of ciprofibrate. The marked increase in total lipid content normally seen after partial hepatectomy was inhibited by ciprofibrate treatment. Vitamin E levels were also reduced in ciprofibrate-fed rats. The activity of the peroxisomal enzyme fatty acyl CoA oxidase was increased in rats fed ciprofibrate at all time points, verifying the induction of peroxisomes by ciprofibrate. This study shows that the administration of 0.025% ciprofibrate before partial hepatectomy inhibits the peak of DNA synthesis normally seen shortly after partial hepatectomy but does not affect the regrowth of the liver. The regrowth of the liver in rats fed 0.025% ciprofibrate may be caused by cellular hypertrophy, as evidenced by the enhanced protein content of the liver.
研究了过氧化物酶体增殖剂环丙贝特对大鼠部分肝切除术后肝脏再生的影响。将环丙贝特以0%、0.01%和0.025%的浓度添加到雌性斯普拉格-道利大鼠的饮食中，持续2周。然后对所有大鼠进行部分肝切除术，并在术后0、12、24、36、48、72和168小时处死。部分肝切除术后，对照组和喂食环丙贝特的大鼠肝脏重量增加速率相似，不过喂食环丙贝特的大鼠肝脏重量始终更高。然而，与对照组大鼠或喂食0.01%环丙贝特的大鼠相比，喂食0.025%环丙贝特的大鼠部分肝切除术后通常出现的DNA合成显著增加受到了部分抑制。在喂食任一浓度环丙贝特的大鼠中，均观察到肝脏中蛋白质与DNA的比值增加。环丙贝特处理抑制了部分肝切除术后通常出现的总脂质含量显著增加。喂食环丙贝特的大鼠维生素E水平也降低。在所有时间点，喂食环丙贝特的大鼠过氧化物酶体酶脂肪酰辅酶A氧化酶的活性均增加，证实了环丙贝特可诱导过氧化物酶体。本研究表明，部分肝切除术前给予0.025%环丙贝特可抑制部分肝切除术后不久通常出现的DNA合成峰值，但不影响肝脏再生。喂食0.025%环丙贝特的大鼠肝脏再生可能是由细胞肥大引起的，肝脏蛋白质含量增加证明了这一点。
