Liver function and pathological changes in Niemann-Pick disease type C1 mice

YANG Ji-chao SONG Ying LIU Da TONG Man ZHANG Yang GUAN Li-hong QIAO Liang* LIN Jun-tang*

doi:10.16098/j.issn.0529-1356.2018.06.009

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Acta Anatomica Sinica ›› 2018, Vol. 49 ›› Issue (6) : 745-751. DOI: 10.16098/j.issn.0529-1356.2018.06.009

Histology,Embryology and Developmental Biology

Liver function and pathological changes in Niemann-Pick disease type C1 mice

YANG Ji-chao^1,5 SONG Ying ^2,5 LIU Da²TONG Man⁴ZHANG Yang⁴ GUAN Li-hong^{2, 5} QIAO Liang ^{2, 5*} LIN Jun-tang ^{3, 5*}

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Abstract

Objective To explore the function and pathology of liver in late Npc1-/-mice (P60) and provide theoretical basis for the pathological and clinical treatment of Niemann-Pick disease type C1 (NPC1). Methods Weighing the mice, the activity of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of eye canthus were analyzed to evaluate liver function of Npc1-/- mouse. The liver tissues were treated with paraffin and then frozen sections and stained HE staining and oil red O staining was used to observe the morphological changes and fat storage in liver tissue. The collagen deposition in liver tissue was evaluated by Masson staining. The Real-time PCR and Western blotting were used to detect the expression of proinflammatory factors interleukin（IL）-1β, IL-6 and tumer necrosis factor(TNF)-α in liver tissue. The apoptosis of liver tissue was observed by TUNEL staining. Results Compared with the Npc1+/+ mouse, the body weight and liver coefficient of Npc1-/- mouse were decreased significantly (P<0.001), and the activity of LDH, ALT and AST were increased significantly (P<0.001). HE staining showed that morphological changes of the liver were obvious in Npc1-/- mice, and a large number of foam cells appeared. Oil red O staining showed a significant decrease in the positive rate of liver fat cells in Npc1-/- mice. Real-time PCR showed that the expression of IL-1β, IL-6 and TNF-α in the liver of Npc1-/- mice increased significantly (P<0.01,P<0.05 andP<0.001). Western blotting showed that the expression of pro-inflammatory factors IL-1β, IL-6 and TNF-α protein increased (P<0.05, P<0.05 and P<0.01); Inflammatory reaction in the late liver; Masson staining showed no obvious collagen deposition in the liver of Npc1-/- mice. TUNEL staining showed that the number of apoptosis cells increased in the liver of Npc1-/- mice. Conclusion The mutation of Npc1 gene leads to the morphological changes of the liver and the amounts of macrophage aggregation. These increases in macrophage aggregation may cause severe inflammatory reactions in the liver. However, the occurrence of inflammatory reactions in liver may play a crucial role in promoting liver cell apoptosis and impaired liver function.

Key words

Niemann-Pick disease type C1 / Liver / Inflammation / Real-time PCR / Western blotting / Mouse

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YANG Ji-chao SONG Ying LIU Da TONG Man ZHANG Yang GUAN Li-hong QIAO Liang LIN Jun-tang. Liver function and pathological changes in Niemann-Pick disease type C1 mice[J]. Acta Anatomica Sinica. 2018, 49(6): 745-751 https://doi.org/10.16098/j.issn.0529-1356.2018.06.009

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