Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasing TIPE2 expression.
Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasing TIPE2 expression.
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血必净注射液通过增加TIPE2表达调节p38 MAPK、MMP-9和HO-1表达对D-半乳糖胺和脂多糖诱导的大鼠急性肝损伤的保护作用。
DOI：
10.3892/ijmm.2016.2749
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发表时间：
2016-11
影响因子：
5.4
通讯作者：
Qian CY
中科院分区：
文献类型：
--
作者：
Liu MW;Liu R;Wu HY;Zhang W;Xia J;Dong MN;Yu W;Wang Q;Xie FM;Wang R;Huang YQ;Qian CY
血必净注射液（XBJ）在中国长期用于治疗感染性疾病。血必净的治疗作用可能与抗炎作用有关。然而，导致XBJ效应的确切机制仍然未知。本研究的目的是为了评估XBJ在D-氨基半乳糖（D-Gal）和脂多糖（LPS）诱导的大鼠急性肝损伤模型中的保护作用。本研究采用D-半乳糖和脂多糖腹腔注射诱导大鼠急性肝损伤。治疗组在给予D-Gal和LPS前2 h静脉滴注XBJ。采用逆转录-定量聚合酶链反应（RT-qPCR）、蛋白质印迹分析、免疫印迹分析、免疫印迹分析等方法，检测了XBJ对D-Gal和LPS诱导的肿瘤坏死因子（TNF）-α诱导蛋白8样2（TIPE 2）、核因子-κB（NF-κB）、基质金属蛋白酶-9（MMP-9）和血红素加氧酶-1（HO-1）表达以及丝裂原活化蛋白激酶（MAPK）信号传导的影响。通过免疫荧光以及通过分析促炎细胞因子和转氨酶、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的血清水平来测定细胞因子的活性。测定肝组织髓过氧化物酶（MPO）、丙二醛（MDA）和超氧化物歧化酶（SOD）的含量。对于组织学分析，评价苏木精和伊红（H&E）染色的肝脏样品。结果表明，XBJ可上调TIPE 2和HO-1的表达，降低NF-κB65和MMP-9的表达，抑制LPS诱导的c-jun N-末端激酶（JNK）和p38 MAPK的基因表达，减少促炎细胞因子[白细胞介素（IL）-6、IL-13和TNF-α]的产生，抑制ALT和AST活性，减轻D-Gal和LPS诱导的肝损伤。组织学结果还表明，XBJ减弱D-半乳糖和LPS诱导的肝脏炎症。结果表明，消必净可能通过上调TIPE 2表达，抑制NF-κB和MAPK信号通路，从而抑制LPS诱导的促炎基因表达，减轻LPS诱导的大鼠肝损伤。血必净对脂多糖所致肝损伤具有明显的保护作用，提示其具有治疗脂多糖所致肝损伤的潜力。
Xuebijing injection (XBJ) has long been used to treat infectious diseases in China. The therapeutic effect of XBJ is probably associated with anti-inflammatory effects. However, the precise mechanisms responsible for the effects of XBJ remain unknown. The present study was conducted in order to evaluate the protective effects of XBJ in a rat model of D-galactosamine (D-Gal)- and lipopolysaccharide (LPS)-induced acute liver injury. In the present study, the rats were injected with D-Gal and LPS intraperitoneally to induce acute liver injury. Two hours prior to D-Gal and LPS administration, the treatment group was administered XBJ by intravenous infusion. The effects of XBJ on D-Gal- and LPS-induced expression of tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2), nuclear factor-κB (NF-κB), matrix metalloproteinase-9 (MMP-9) and heme oxygenase-1 (HO-1) as well as mitogen-activated protein kinase (MAPK) signaling was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis, immunofluorescence, as well as by analysing the serum levels of pro-inflammatory cytokines and the transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the rat liver tissues were also measured. For histological analysis, hematoxylin and eosin (H&E)-stained liver samples were evaluated. The results showed that XBJ upregulated TIPE2 and HO-1 expression, reduced the expression of NF-κB65 and MMP-9, inhibited the LPS-induced gene expression of c-jun N-terminal kinase (JNK) and p38 MAPK, decreased the generation of pro-inflammatory cytokines [interleukin (IL)-6, IL-13 and TNF-α], inhibited ALT and AST activity, and ameliorated D-Gal- and LPS-induced liver injury. The histological results also demonstrated that XBJ attenuated D-Gal- and LPS-induced liver inflammation. It was found that XBJ may prevent LPS-induced pro-inflammatory gene expression through inhibiting the NF-κB and MAPK signaling pathways by upregulating TIPE2 expression, thereby attenuating LPS-induced liver injury in rats. The marked protective effects of XBJ suggest that it has the potential to be used in the treatment of LPS-induced liver injury.
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