Mechanism of aerobic exercise treating liver fibrosis in mouse models of obstructive jaundice

doi:10.3969/j.issn.2095-4344.1387

Abstract

Abstract:

BACKGROUND: Hepatocyte apoptosis or necrosis due to cholestasis after obstructive jaundice can induce chronic liver injury. Liver fibrosis is a repairing reaction, which may cause pathological changes, such as liver dysfunction and liver tissue sclerosis.
OBJECTIVE: To analyze the relationship between the expression of gene LincRNA-p21 in liver tissue of obstructive jaundice mice and its biological function, and to explore the mechanism of LincRNA-p21 through the Notch pathway improving liver fibrosis in obstructive jaundice mice after aerobic exercise.
METHODS: Thirty-five male ICR mice were provided by Hunan Slack Jingda Experimental Animal Co., Ltd., and the study was approved by the Ethics Committee of Hunan Normal University, approval No. 2018-183. All mice were used to construct the obstructive jaundice model with the common bile duct hanged on the abdominal wall. Five mice were randomly selected to testify whether the modeling is successful. The remaining 30 mice were randomly divided into aerobic exercise, model, and control groups. The aerobic exercise group underwent treadmill adaptive training for 1 week. At 1-2 days, the treadmill slop was 0° with the speed of 6 m/min, 20 min/d. At 3-4 days, the treadmill slop was 5° with the speed of 8 m/min, 40 min/d. At 5-6 days, the treadmill slop was 8° with the speed of 10 m/min, 60 min/d. After adaptive training, the treadmill slop was kept at 8° with the speed of 10 m/min, 60 min/d, and 6 d/week. The samples were removed under anesthesia at 7 days to detect each index.
RESULTS AND CONCLUSION: (1) Compared with the control group, the serum concentrations of total bilirubin, total bile acid, glutamate pyruvate transaminase, glutamic oxalacetic transaminase and alkaline phosphatase were significantly increased in the model group (P < 0.01). The aerobic exercise group showed different degrees of reduction compared with the model group (P < 0.05, P < 0.01). (2) In the model group, hematoxylin-eosin staining showed the hepatocytes with large-area fibrosis and disordered hepatic cord, vacuolar, degeneration and necrotic symptoms. The fibrosis degree in the aerobic exercise group was lower than that in the model group. (3) Compared with the model group, the expression levels of LincRNA-p21 protein and mRNA in the aerobic exercise and control groups were increased (P < 0.01), and the control group was higher than in the aerobic exercise group. The expression levels of Notch-1, Jagged-1, NICD, and HES-1 protein and mRNA were highest in the model group (P < 0.01), followed by aerobic exercise group. (4) To conclude, aerobic exercise can promote the high expression of LincRNA-p21, thereby inhibiting the Notch pathway to participate in the process of liver fibrosis in mice after obstructive jaundice, and can regulate the repair after liver injury to some extent.

Key words: aerobic exercise, LincRNA-p21, Notch signaling pathway, obstructive jaundice, liver fibrosis, mice

CLC Number:

Peng Rui1, Chen Wei2, Mao Haifeng1, Zhang Yu1. Mechanism of aerobic exercise treating liver fibrosis in mouse models of obstructive jaundice[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(27): 4369-4374.

Figures/Tables 3

2.1 实验动物数量分析实验选用造模成功小鼠30只，实验过程无脱失，全部进入结果分析。 2.2 一般行为学观察及建模成功标准构建模型72 h后。小鼠尿液颜色加深，粪便显浅灰色或陶土色，四肢、尾及胸腹部肤色暗黄，下背部存在显著咬痕且有挠痒行为，但食欲、运动能力正常。随机抽取构模小鼠5只，剖腹检查发现胆总管悬挂近端出现囊性扩张且肝脏呈淤胆样改变。取肝组织进行苏木精-伊红染色，其肝索、肝细胞均有结构性改变。故判断此模型构建成功。运动干预期间，共记录12次，发现模型组黄染程度加重或出现绿褐色，食欲下降，排泄物颜色显著加深，四肢呈现无力；有氧运动组毛发及肤色趋向正常，排泄物颜色变浅，攀爬能力相比模型组增强。 2.3 肝脏病理学观察由图1肝脏苏木精-伊红染色结果可知，细胞核呈蓝色，细胞浆被伊红染成深浅不同的粉红色。胶原纤维及弹力纤维发生病变时，伊红着色由浅变深。相比空白组，模型组肝细胞索结构紊乱，肝细胞出现大量纤维化，间隙扩张，细胞外基质有沉积现象，核固缩、空泡显著增多，胞核缺乏完整度，存在片状肝细胞坏死现象。有氧运动组肝细胞纤维化程度显著降低，肝索排列较整齐。肝小叶结构欠规则，有少量空泡，肝细胞纤维化得到改善。空白组肝索呈现放射状，无纤维化症状。 2.4 血清学指标检测由表2可知，模型组血清中总胆红素、总胆汁酸、谷丙转氨酶、谷草转氨酶、碱性磷酸酶蛋白含量最高，空白组最低。相比模型组，有氧运动组、空白组各指标蛋白水平差异有非常显著性意义(P < 0.01)；相比有氧运动组，空白组各指标蛋白水平差异有非常显著性意义(P < 0.01)。 "

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