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卜浩林,李丽红,李 欣,郭建红.长期高蛋白饮食对 OVX 小鼠肝脂肪变性和脂肪堆积的影响[J].中国比较医学杂志,2021,31(11):69~75.
长期高蛋白饮食对 OVX 小鼠肝脂肪变性和脂肪堆积的影响
Long-term intake of a high protein diet modulates liver steatosis and fat accumulation in OVX mice
投稿时间:2020-11-27  
DOI:10. 3969 / j.issn.1671-7856. 2021. 11. 011
中文关键词:  卵巢切除  高蛋白饮食  肝脂肪变性  GLP-1  SREBP-1c  小鼠
英文关键词:ovariectomy  high protein diet  liver steatosis  GLP-1  SREBP-1c  mice
基金项目:
作者单位E-mail
卜浩林 1.山西医科大学病理生理学教研室,太原 030001
2.山西医科大学肝病研究所,太原 030001 
370487549@ qq.com 
李丽红 1.山西医科大学病理生理学教研室,太原 030001
2.山西医科大学肝病研究所,太原 030001 
 
李 欣 1.山西医科大学病理生理学教研室,太原 030001
2.山西医科大学肝病研究所,太原 030001 
 
郭建红 1.山西医科大学病理生理学教研室,太原 030001
2.山西医科大学肝病研究所,太原 030001 
sgs7551@ 126.com 
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中文摘要:
       目的 探讨长期高蛋白饮食对卵巢切除(ovariectomy, OVX)小鼠肝、脂肪组织的影响及胰高血糖素样肽-1(glucagon-like peptide-1, GLP-1)的作用。 方法 32 只 8 周龄 C57BL/ 6 雌性小鼠随机分为对照(Control)组、模型(OVX)组、高蛋白(OVX+HP)组、低蛋白(OVX+LP)组,每组 8 只,模型组、高蛋白组、低蛋白组小鼠行卵巢切除后分别给予标准饮食、高蛋白饮食、低蛋白饮食;对照组进行相同手术保留卵巢,给以标准饮食。每周称量小鼠体重,于 24 周末处死后,取肝、结肠、腹膜后脂肪组织,并称重脂肪组织;HE 染色观察肝、腹膜后脂肪的病理改变; 酶联免疫吸附测定(ELISA)法检测血清中 GLP-1 的含量;实时定量 PCR 检测肝固醇调节元件结合蛋白-1c( sterol regulatory element binding protein-1c, SREBP-1c)以及结肠组织中 GLP-1 mRNA 的表达,免疫组织化学染色法检测肝 SREBP-1c 蛋白的表达。 结果 24 周末,与对照组相比,模型组体重增加( P< 0. 05)、腹膜后脂肪组织增多( P< 0. 05);HE 染色模型组肝细胞内可见大量脂滴、腹膜后脂肪组织细胞体积增大;结肠组织中 GLP-1 mRNA 表达降低 (P<0. 05),血浆中 GLP-1 含量减少(P<0. 05),肝组织中 SREBP-1c 的 mRNA 表达升高(P<0. 05),SREBP-1c 蛋白表达增多;高蛋白组与模型组相比,体重降低(P<0. 01),腹膜后脂肪显著减少(P<0. 001),病理切片肝细胞内可见少量脂滴、腹膜后脂肪细胞体积缩小;结肠组织 GLP-1 mRNA 表达升高(P< 0. 01),血浆中 GLP-1 含量增多(P< 0. 001),肝 SREBP-1c 的 mRNA 表达降低(P<0. 001),SREBP-1c 蛋白表达减少;低蛋白组与模型组在体重、腹膜后脂肪以及 GLP-1、SREBP-1c 的 mRNA 表达方面差异无统计学意义。 结论 长期高蛋白饮食可以改善 OVX 小鼠体重增加和肝脂肪变性,这可能与高蛋白饮食促进肠道分泌 GLP-1、下调肝 SREBP-1c 的 mRNA 及蛋白表达,发挥类似雌激素的作用有关。
英文摘要:
       Objective To explore the effect of a long-term high protein diet on liver and adipose tissues of ovariectomy (OVX) mice and the role of glucagon-like peptide-1 (GLP-1). Methods 32 8-week-old C57BL/ 6 female mice were randomly divided into control (Control), model (OVX), high protein (OVX+HP) and low protein (OVX+LP) groups with eight rats in each group. After ovariectomied, OVX, OVX + HP and OVX + LP groups were provided with standard, high protein and low protein diets, respectively. The control group received the same operation to preserve the ovaries and were provided with a standard diet. The mice were weighed weekly and sacrificed at the end of 24th week. The liver, colon and retroperitoneal adipose tissue were collected, and retroperitoneal adipose tissue was weighed. HE staining was used to observe pathological changes of the liver and retroperitoneal adipose tissue. An enzyme-linked immunosorbent assay was used to measure serum GLP-1 levels. Real-time quantitative PCR was used to measure the expression of sterol regulatory element-binding protein-1c (SREBP-1c) in the liver and GLP-1 in colon tissues. Immunohistochemical staining was used to detect expression of SREBP-1c protein in the liver. Results At the end of 24th week, compared with the control group, the OVX group gained weight (P<0. 05) and retroperitoneal adipose tissue was increased (P<0. 05). A large number of lipid droplets in hepatocytes and the retroperitoneal adipocyte volume were increased in the OVX group. GLP-1 mRNA expression in colon tissues of the OVX group was decreased (P<0. 05), and the serum GLP-1 content in the OVX group was also decreased (P<0. 05). SREBP-1c mRNA and protein expression in liver tissues was increased in the OVX group (P<0. 05). Compared with the OVX group, the OVX+HP group showed a decrease in body weight (P<0. 01) and a significant decrease in retroperitoneal adipose tissue (P<0. 001). A small amount of lipid droplets was observed in hepatocytes, and retroperitoneal adipose cells had shrunk in pathological sections of the OVX+HP group. GLP-1 mRNA expression in colon tissues was increased in the OVX + HP group ( P< 0.01). Serum GLP-1 content was significantly increased in the OVX+HP group (P<0. 001). SREBP-1c mRNA and protein expression in liver was decreased in the OVX +HP group ( P < 0. 001). There was no statistically significant difference in weight, retroperitoneal fat and the mRNA expression of GLP-1 and SREBP-1c between OVX+ LP and OVX groups. Conclusions A long-term high protein diet improved weight gain and liver steatosis in OVX mice, which may be related to the high protein diet promoting GLP-1 secretion in intestines and downregulating the protein expression of SREBP-1c in the liver, which plays a similar role to estrogen.
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