Splenectomy reduces fibrosis and preneoplastic lesions with increased triglycerides and essential fatty acids in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet
Splenectomy reduces fibrosis and preneoplastic lesions with increased triglycerides and essential fatty acids in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet
复制标题
DOI：
10.1111/j.1872-034x.2011.00784.x
复制
发表时间：
2011-05-01
影响因子：
4.2
通讯作者：
Sakaida, Isao
中科院分区：
文献类型：
--
作者：
Oishi, Toshiyuki;Terai, Shuji;Sakaida, Isao
目的：本研究探讨脾切除术对非酒精性脂肪性肝炎（NASH）是否具有重要意义。方法：5周龄Wistar大鼠饲喂缺乏胆碱的饲料8周，建立NASH模型。然后进行假手术或脾切除，4周后处死大鼠。结果：与假手术组相比，脾切除组肝纤维化和肝脏癌前病变明显减少，α平滑肌肌动蛋白（SMA）表达显着抑制（肝纤维化面积：假手术组8.63+/-4.09%，脾切除5.45+/-3.69%，P < 0.01；瘤前病变大小：假手术 6.56 +/- 3.68 x106 mu m2/cm2，脾切除 4.63 +/- 3.27 x106 mu m2/cm2，P < 0.05；瘤前病变数量：假手术 8.33 +/- 3.96/cm2，脾切除 5.17 +/- 1.80/cm2，P < 0.01；α-平滑肌肌动蛋白阳性面积：假手术组 4.41 +/- 2.48%，脾切除组 2.75 +/- 1.66%，P < 0.01) 另一方面，脾切除组的肝脏甘油三酯和必需脂肪酸显着升高（肝脏甘油三酯：假手术组 182 +/- 35.0） mg/g，脾切除术 230 +/- 35.0 mg/g，P < 0.05；假手术组 17.2 +/- 4.9 mg/g，脾切除术 23.3 +/- 6.9 mg/g，P < 0.05；肝脏 α-亚麻酸：假手术组 118 +/- 36.6 μg/g，脾切除术 162 +/- 51.4μg/g，P<0.05）。此外，脾切除组肝脏脂肪酸代谢相关基因（如酰基辅酶A氧化酶、肝肉毒碱棕榈酰辅酶A转移酶I、细胞色素P450 4A、长链酰基辅酶A脱氢酶和中链酰基辅酶A脱氢酶）的表达显着受到抑制。大鼠胆碱缺乏L-氨基酸模型中肝脏的病变和脂质代谢。
Aim:This study investigated whether splenectomy is of significance in non-alcoholic steatohepatitis (NASH).Methods:Five-week-old Wistar rats were fed a choline-deficient diet for 8 weeks to create a NASH model. A sham-operation or splenectomy was then performed, and rats were killed 4 weeks later.Results:Liver fibrosis and liver preneoplastic lesions were significantly reduced in the splenectomy group compared to the sham-operation group, and alpha-smooth muscle actin (SMA) expression was significantly inhibited (liver fibrosis area: sham 8.63 +/- 4.09%, splenectomy 5.45 +/- 3.69%, P < 0.01; preneoplastic lesion size: sham 6.56 +/- 3.68 x106 mu m2/cm2, splenectomy 4.63 +/- 3.27 x106 mu m2/cm2, P < 0.05; the number of preneoplastic lesions: sham 8.33 +/- 3.96/cm2, splenectomy 5.17 +/- 1.80/cm2, P < 0.01; alpha-smooth muscle actin-positive area: sham 4.41 +/- 2.48%, splenectomy 2.75 +/- 1.66%, P < 0.01) On the other hand, liver triglycerides and essential fatty acids were significantly increased in the splenectomy group (liver triglycerides: sham 182 +/- 35.0 mg/g, splenectomy 230 +/- 35.0 mg/g, P < 0.05; liver linoleic acid: sham 17.2 +/- 4.9 mg/g, splenectomy 23.3 +/- 6.9 mg/g, P < 0.05; liver alpha-linolenic acid: sham 118 +/- 36.6 mu g/g, splenectomy 162 +/- 51.4 mu g/g, P < 0.05). In addition, expressions of hepatic fatty acid metabolism-related genes (e.g. acyl-CoA oxidase, liver carnitine palmitoyl-CoA transferase I, cytochrome P450 4A, long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase) were significantly inhibited in the splenectomy group.Conclusion:These findings suggest that spleen plays an important regulatory role in the fibrosis, preneoplastic lesion and lipid metabolism of liver in a rat choline-deficient L-amino acid model.