离体灌注肝脏模型：大鼠与豚鼠的比较

Isolated perfused liver model: the rat and guinea pig compared.

作者信息

Chaïb Samira, Charrueau Christine, Neveux Nathalie, Coudray-Lucas Colette, Cynober Luc, De Bandt Jean-Pascal

机构信息

Laboratoire de Biologie de la Nutrition EA 2498, Faculté de Pharmacie, Laboratoire de Biochimie A, Hôpital Hôtel-Dieu AP-HP, Paris, France.

出版信息

Nutrition. 2004 May;20(5):458-64. doi: 10.1016/j.nut.2004.01.011.

DOI:10.1016/j.nut.2004.01.011

PMID:15105034

Abstract

OBJECTIVE

Although the rat is the most commonly used species for the study of hepatic metabolism, the physiology of the guinea pig is closer to human physiology. We compared the model of isolated perfused guinea pig liver with the classic model of isolated perfused rat liver, especially with respect to amino acid metabolism.

METHODS

After validation of an anesthetic mixture of ketamine, diazepam, and xylazine for the guinea pig, isolated perfused livers were harvested for both species. Three groups of animals were compared for the study of liver metabolic fluxes: 6-wk-old male Sprague-Dawley rats (R; 230 +/- 10 g, n = 5), young male Hartley guinea pigs (YG; 223 +/- 8 g, n = 6) matched to rats by liver weight, and adult male Hartley guinea pigs (AG; 389 +/- 5 g, n = 6) matched to rats by age. Results (mean +/- standard error of the mean) were compared by analysis of variance and Newman-Keuls tests.

RESULTS

Both models displayed a satisfactory hepatic viability, but differences were noted, with higher portal flows (R: 3.1 +/- 0.3 versus YG: 4.5 +/- 0.3 and AG: 4.2 +/- 0.3 mL. min(-1). g(-1); P < 0.05, YG and AG versus R) and bile flows (R: 0.34 +/- 0.01 versus YG: 2.38 +/- 0.22 versus AG: 3.17 +/- 0.28 microL. min(-1). g(-1); P < 0.05, YG and AG versus R, and YG versus AG) and higher amino acid fluxes (P < 0.05) leading to greater nitrogen uptake (P < 0.05) in guinea pigs. We performed a second set of experiments to evaluate the influence of anesthesia and portal flow on this last parameter. In these experiments, rats were anesthetized with ketamine, diazepam, and xylazine and guinea pig livers were perfused at rat blood flow. Apart from a 50% anesthesia-related mortality for rats, bile flow and metabolic parameters were only slightly modified. However, some amino acid fluxes were statistically different (aspartate, serine, and histidine; P < 0.05), as confirmed by a higher transfer constant.

CONCLUSION

Our results indicate that the isolated perfused guinea pig liver is a suitable model for the study of hepatic metabolism.

摘要

目的

虽然大鼠是研究肝脏代谢最常用的物种，但豚鼠的生理学特性更接近人类生理学。我们比较了离体灌注豚鼠肝脏模型与经典的离体灌注大鼠肝脏模型，特别是在氨基酸代谢方面。

方法

在验证了氯胺酮、地西泮和赛拉嗪的麻醉混合物对豚鼠有效后，收集了两种物种的离体灌注肝脏。比较了三组动物的肝脏代谢通量：6周龄雄性斯普拉格-道利大鼠（R组；230±10 g，n = 5）、肝脏重量与大鼠匹配的年轻雄性哈特利豚鼠（YG组；223±8 g，n = 6）以及年龄与大鼠匹配的成年雄性哈特利豚鼠（AG组；389±5 g，n = 6）。通过方差分析和纽曼-丘尔斯检验比较结果（平均值±平均值标准误差）。

结果

两种模型均显示出令人满意的肝脏活力，但存在差异，豚鼠的门静脉血流量（R组：3.1±0.3 对比 YG组：4.5±0.3 和AG组：4.2±0.3 mL·min⁻¹·g⁻¹；P < 0.05，YG组和AG组对比R组）和胆汁流量（R组：0.34±0.01 对比 YG组：2.38±0.22 对比AG组：3.17±0.28 μL·min⁻¹·g⁻¹；P < 0.05，YG组和AG组对比R组，以及YG组对比AG组）更高，氨基酸通量也更高（P < 0.05），导致豚鼠的氮摄取量更大（P < 0.05）。我们进行了第二组实验，以评估麻醉和门静脉血流对最后一个参数的影响。在这些实验中，大鼠用氯胺酮、地西泮和赛拉嗪麻醉，豚鼠肝脏以大鼠血流灌注。除了大鼠有50%与麻醉相关的死亡率外，胆汁流量和代谢参数仅略有改变。然而，一些氨基酸通量在统计学上有差异（天冬氨酸、丝氨酸和组氨酸；P < 0.05），较高的转移常数证实了这一点。