多氯联苯118诱导大鼠非酒精性脂肪肝病的研究
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国家自然科学基金(81670724)


Polychlorinated biphenyl 118 induced nonalcoholic fatty liver disease in rats
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    摘要:

    目的:探讨慢性低浓度多氯联苯118(polychlorinated biphenyl 118,PCB118)是否引起大鼠非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)及其机制。方法:Wistar大鼠随机分为4组,腹腔注射PCB118[10、100和1 000 μg/(kg·d)]或玉米油[0.5 mL/(kg·d)]13周。检测血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、葡萄糖(GLU)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平及白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶-2(MMP-2)、α-平滑肌肌动蛋白(α-SMA)mRNA 表达水平。HE及天狼星红染色观察肝脏脂肪变性、炎症细胞浸润及纤维化程度。结果:不同浓度PCB118刺激后与对照组比较,血清ALT、TG、TC、GLU、LDL-C、HDL-C水平显著增加(P < 0.01),血清AST水平略有增加但差异无统计学意义。IL-1β、TNF-α、TGF-β1、MMP-2、α-SMA mRNA水平显著增加(P<0.05)。HE 染色示肝脏脂肪变性、炎症浸润,天狼星红染色示肝小叶结构紊乱,明显纤维化。结论:慢性低浓度PCB118通过炎症机制促进肝脏纤维化,诱导大鼠NAFLD发生。

    Abstract:

    Objective:To explore whether chronic low-dose polychlorinated biphenyl 118(PCB118)could induce nonalcoholic fatty liver disease(NAFLD)in rats. Methods:Wistar rats were randomly divided into 4 groups and injected intraperitoneally with PCB118[10,100 or 1 000 μg/(kg·d)]or corn oil[0.5 mL/(kg·d)]for 13 weeks,respectively. Serum levels of alanine transaminase(ALT),aspartate aminotransferase(AST),glucose(GLU),triglyceride(TG),total Cholesterol(TC),low-density lipoproteincholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c)were measured,and the mRNA expresion of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and fibrogenic factor transforming growth factor-β1(TGF-β1),matrix metalloproteinase-2(MMP-2),α-smooth muscle actin(α-SMA)were quantified. Hepaticsteatosis,inflammatory cell infiltration and liver fibrosis were observed by HE staining and Sirius red staining,respectively. Results:Compared to control group,after stimulation with different concentrations of PCB118,serum ALT,TG,TC,GLU,LDL-C,HDL-C levels were significantly increased(P < 0.01),and serum AST level was slightly increased,but no statistical significance was observed(P > 0.05). The mRNA expression levels of IL-1β,TNF-α,TGF-β1,MMP-2 and α-SMA increased,and were significantly different compared with the control group(P < 0.05). HE staining showed steatosis and inflammation in the liver of rats in PCB118-treated group was more serious than that in the control group,and Sirius red staining showed that the hepatic lobule structure was disordered with obvious red staining area in PCB118 treatment group. Conclusion:Chronic low-concentration PCB118 could promote liver fibrosis through inflammatory mechanisms and induce NAFLD in rats.

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周 琪,许文立,王 莉,段 宇.多氯联苯118诱导大鼠非酒精性脂肪肝病的研究[J].南京医科大学学报(自然科学版),2019,(5):659-663

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  • 收稿日期:2019-02-13
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  • 在线发布日期: 2019-05-31
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