外源性瘦素对梗阻性黄疸大鼠肠黏膜增殖的影响

doi:10.3877/cma.j.issn.1674-0785.2023.05.013

中华临床医师杂志(电子版) ›› 2023, Vol. 17 ›› Issue (05) : 575 -580. doi: 10.3877/cma.j.issn.1674-0785.2023.05.013

基础研究

外源性瘦素对梗阻性黄疸大鼠肠黏膜增殖的影响

方辉, 李菲, 张帆, 魏强, 陈强谱^†(

)

256600　山东省滨州市；滨州医学院附属医院放射科；256600　山东省临床营养与代谢重点实验室
256600　山东省滨州市；滨州医学院附属医院肝胆外科
256600　山东省滨州市；滨州医学院附属医院肝胆外科；256600　山东省临床营养与代谢重点实验室
256600　山东省滨州市；滨州医学院附属医院肝胆外科；256600　山东省滨州市；滨州医学院附属医院临床营养科；256600　山东省临床营养与代谢重点实验室

收稿日期:2022-03-30 出版日期:2023-05-15
通信作者: 陈强谱
基金资助:
山东省省级临床重点专科学科建设基金资助项目(SLCZDZK-2401)

Effect of exogenous leptin on intestinal mucosal proliferation in rats with obstructive jaundice

Hui Fang, Fei Li, Fan Zhang, Qiang Wei, Qiangpu Chen^†()

Department of Radiology, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China; Clinical Nutrition and Metabolism Key Laboratory, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China
Department of Hepatobiliary Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China
Department of Hepatobiliary Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China; Clinical Nutrition and Metabolism Key Laboratory, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China
Department of Hepatobiliary Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China; Department of Clinical Nutrition, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China; Clinical Nutrition and Metabolism Key Laboratory, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China

Received:2022-03-30 Published:2023-05-15
Corresponding author: Qiangpu Chen

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引用本文：

方辉, 李菲, 张帆, 魏强, 陈强谱. 外源性瘦素对梗阻性黄疸大鼠肠黏膜增殖的影响[J]. 中华临床医师杂志(电子版), 2023, 17(05): 575-580.

Hui Fang, Fei Li, Fan Zhang, Qiang Wei, Qiangpu Chen. Effect of exogenous leptin on intestinal mucosal proliferation in rats with obstructive jaundice[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(05): 575-580.

目的

探讨外源性瘦素对梗阻性黄疸大鼠肠黏膜增殖的影响。

方法

采用由32只Wistar大鼠制成的完全梗阻性黄疸模型，随机分成2组：对照组（C组）、研究组（S组），每组16只。S组大鼠自术后第1 d腹腔注射重组瘦素10 ug/kg，bid，C组大鼠相应时间点腹腔注射等量生理盐水。2组大鼠分别于术后5 d和8 d各处死8只，形成C5组、C8组、S5组和S8组。观察大鼠的一般状况；HE染色观察肠黏膜组织形态学改变及肠黏膜绒毛高度和隐窝深度；免疫组化法检测肠黏膜瘦素及其受体受体和Ki67抗原表达。

结果

肠黏膜细胞增殖变化：C8组的肠黏膜增殖指数明显低于S8组，P＜0.01，C5组的肠黏膜增殖指数明显低于S5组，P＜0.01；C5组的肠黏膜增殖指数高于C8组，S5组的肠黏膜增殖指数高于S8组。肠黏膜瘦素蛋白及其瘦体变化：C8组的肠黏膜OB蛋白表达明显低于S8组，P＜0.05，C5组的肠黏膜OB蛋白表达明显低于S5组，P＜0.01；C5组的OB蛋白表达高于C8组，S5组的OB蛋白表达高于S8组。C8组的瘦素受体表达明显低于S8组，P＜0.05，C5组的瘦素受体表达明显低于S5组，P＜0.01；C5组的瘦素受体表达高于C8组，S5组的瘦素受体表达高于S8组。

结论

外源性瘦素可促进对梗阻性黄疸大鼠肠黏膜的细胞增殖、减轻肠黏膜损害。

关键词: 瘦素, 梗阻性黄疸, 肠黏膜, 增殖

Objective

To explore the effect of exogenous leptin on the proliferation of the intestinal mucosa in rats with obstructive jaundice.

Methods

Obstructive jaundice was induced by surgery in 32 Wistar rats, which were then randomly divided into either a control group or a study group, with 16 rats in each group. The study group was given recombinant leptin (10 μg/kg, bid) by intraperitoneal injection after operation, while the control group was injected with equal volume of saline. Rats in each group were sacrificed at 5 days and 8 days, and then labeled as C5 group, C8 group, S5 group, and S8 group, respectively. The general conditions of the rats were observed. Intestinal mucosal tissues were stained with hematoxylin-eosin (HE), and the changes of intestinal mucosal morphology and damage were observed. Immunohistochemistry (IHC) was used to detect the expression of leptin, leptin receptor, and Ki67 in the intestinal mucosa.

Results

The intestinal mucosal injury index was significantly lower in the control group than in the study group, while it was significantly higher in the C5 and S5 groups than in the C8 and S8 groups. The expression of leptin and leptin receptor in the control group was significantly lower than that in the study group, while it was significantly higher in the C5 and S5 groups than that in the C8 and S8 groups, respectively.

Conclusion

Exogenous leptin has the effect of promoting the proliferation and mitigate the damage of intestinal mucosal cells in rats with obstructive jaundice.

Key words: Leptin, Obstructive jaundice, Intestinal mucosa, Proliferation

图1 不同组别大鼠肠黏膜组织形态学改变。图a为C5组肠黏膜形态改变HE（×100）；图b为C8组肠黏膜形态改变HE（×100）；图c为S5组肠黏膜形态改变HE（×100）；图d为S8组肠黏膜形态改变HE（×100）

表1 不同组别大鼠肠黏膜绒毛高度的测量（μm，

x ¯

±s）

组别	C组	S组	F值	P值
5 d	528.89±226.71	577.26±169.71^a	4.772	=0.01
8 d	486.94±192.52	494.57±88.32^a	61.971	＜0.01

表1 不同组别大鼠肠黏膜绒毛高度的测量（μm，

x ¯

±s）

组别	C组	S组	F值	P值
5 d	528.89±226.71	577.26±169.71^a	4.772	=0.01
8 d	486.94±192.52	494.57±88.32^a	61.971	＜0.01

表2 不同组别大鼠肠黏膜隐窝深度的测量（μm，

x ¯

±s）

分组	C组	S组	F值	P值
5 d	198.23±70.26	236.89±46.22^a	14.760	=0.01
8 d	186.3±105.87	242.17±85.77^a	22.188	＜0.01

表2 不同组别大鼠肠黏膜隐窝深度的测量（μm，

x ¯

±s）

分组	C组	S组	F值	P值
5 d	198.23±70.26	236.89±46.22^a	14.760	=0.01
8 d	186.3±105.87	242.17±85.77^a	22.188	＜0.01

表3 不同组别大鼠肠黏膜增殖指数Ki67的表达（

x ¯

±s）

组别	C组	S组	F值	P值
5 d	0.0815±0.0310	0.1340±0.0418^a	4.596	＜0.05
8 d	0.0791±0.0238	0.1252±0.0188^a	8.635	＜0.01

表3 不同组别大鼠肠黏膜增殖指数Ki67的表达（

x ¯

±s）

组别	C组	S组	F值	P值
5 d	0.0815±0.0310	0.1340±0.0418^a	4.596	＜0.05
8 d	0.0791±0.0238	0.1252±0.0188^a	8.635	＜0.01

图2 不同组别大鼠肠黏膜增殖指数Ki67的表达。图a为C5组肠黏膜Ki67的表达（×100）；图b为C8组肠黏膜Ki67的表达（×100）；图c为S5组肠Ki67的表达（×100）；图d为S8组肠Ki67的表达（×100）

表4 不同组别大鼠肠黏膜OB蛋白的表达（

x ¯

±s）

组别	C组	S组	F值	P值
5 d	0.2931±0.0652	0.3954±0.0390^a	7.125	＜0.01
8 d	0.2810±0.0752	0.3615±0.0888^a	6.345	＜0.01

表4 不同组别大鼠肠黏膜OB蛋白的表达（

x ¯

±s）

组别	C组	S组	F值	P值
5 d	0.2931±0.0652	0.3954±0.0390^a	7.125	＜0.01
8 d	0.2810±0.0752	0.3615±0.0888^a	6.345	＜0.01

图3 不同组别大鼠肠黏膜OB蛋白的表达。图a为C5组肠黏膜OB表达（×100）图b为C8组肠黏膜OB表达（×100）图c为S5组肠黏膜OB表达（×100）图d为S8组肠黏膜OB表达（×100）

表5 不同组别大鼠肠黏膜瘦素受体（LP-R）的表达（

x ¯

±s）

分组	C组	S组	F值	P值
5 d	0.2696±0.0708	0.3690±0.0216^a	6.045	＜0.01
8 d	0.2599±0.0553	0.3436±0.0732^a	5.756	＜0.01

表5 不同组别大鼠肠黏膜瘦素受体（LP-R）的表达（

x ¯

±s）

分组	C组	S组	F值	P值
5 d	0.2696±0.0708	0.3690±0.0216^a	6.045	＜0.01
8 d	0.2599±0.0553	0.3436±0.0732^a	5.756	＜0.01

图4 不同组别大鼠肠黏膜瘦素受体（LP-R）的表达。图a为C5组肠黏膜LP-R的表达（×100）图b为C8组肠黏膜LP-R的表达（×100）图c为S5组肠黏膜LP-R的表达（×100）图d为S8组肠黏膜LP-R的表达（×100）

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