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2009 2

2008 1

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Protective effect of N-acetylcysteine against lipopolysaccharide injury in hepatocytes of neonatal mice

WANG Lin, LIU Yalan, XU Jianbo, TIAN Yuan, WU Heshui

《医学前沿(英文)》 2008年 第2卷 第2期   页码 182-185 doi: 10.1007/s11684-008-0034-x

摘要: The present study provides supportive evidence for the effective prevention and treatment of lipopolysaccharide (LPS)-induced hepatocyte injury in neonatal mice by N-acetylcysteine (NAC). Hepatocytes of neonatal mice were obtained through collagenase digestion of the liver. The hepatocytes were treated either with LPS (10 ?g/mL) alone or with NAC (5 mmol/L) for 1 h before the addition of LPS (10 ?g/mL). After LPS treatment, 12 wells of the cultured hepatocytes and supernatants were harvested at 0, 6, and 12 h, respectively. Levels of alanine aminotransferase (ALT) and nitric oxide (NO) in the supernatant were biochemically quantified and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the expression of inducible nitric oxide synthase (iNOS) mRNA after different treatments. At 0 h following the treatment of primary cultured hepatocytes with LPS, the levels of ALT, NO and iNOS mRNA in the supernatant were (21.1 ± 4.78) u/L, (1.6 ± 0.31) ?mol/L and 0.17 ± 0.023, respectively; at 6 h, (59.8 ± 8.59) u/L, (6.6 ± 0.81) ?mol/L, and 0.71 ± 0.091; and at 12 h, (89.6 ± 15.30) u/L, (7.8 ± 1.01) ?mol/L, and 0.71 ± 0.097. The levels of ALT, NO and iNOS mRNA at 6 and 12 h increased significantly, compared to those at 0 h ( < 0.01). In contrast to LPS treatment alone, pretreatment with NAC before LPS addition significantly reduced the levels of ALT, NO and iNOS mRNA in the supernatant at 6 h to (40.8 ± 7.30) u/L, (3.2 ± 0.71) ?mol/L, and 0.41 ± 0.060; and at 12 h to (55.4 ± 5.48) u/L, (4.0 ± 0.71) ?mol/L, and 0.40 ± 0.067, respectively ( < 0.01). However, the levels of ALT, NO and iNOS mRNA at 0 h did not change significantly with both treatment approaches. NAC has protective effects in hepatocytes of neonatal mice against LPS-induced injury as shown by the reduced levels of ALT, NO and iNOS mRNA when primary hepatocytes were treated with NAC prior to LPS stimulation. We postulate that NAC exhibits its protective function by inhibiting LPS-induced transcription of iNOS, resulting in decreased levels of NO.

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

《医学前沿(英文)》 2021年 第15卷 第2期   页码 292-301 doi: 10.1007/s11684-020-0806-5

摘要: The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA+LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor- B (NF- B), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the anti-inflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and . B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, I Bα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.

关键词: bioactive hyaluronan     lipopolysaccharide     inflammatory cytokines     TLR4     human macrophages    

Effect of decoction on CD14 expression in lipopolysaccharide signal transduction pathway of alcohol-induced

Rui ZHU MD , Lin SHEN MD , Jianguo LIU MD , Weili ZHANG MM , Ling YANG MD ,

《医学前沿(英文)》 2009年 第3卷 第3期   页码 363-367 doi: 10.1007/s11684-009-0064-z

摘要: This paper aims to investigate the effects of (枳黄) decoction on CD14 expression in the lipopolysaccharide signal transduction pathway of alcohol-induced liver disease in rats. Seventy-five Wistar rats were randomly divided into three groups. Ethanol (56%, weight/volumn) was intragastrically administrated to 50 rats (14mL/kg body weight per day) for 10 days to establish a model of alcohol-induced liver disease, and 25 of these 50 rats were treated with decoction simultaneously. Liver injury was evaluated by biochemical examination. The plasma content of endotoxin was assayed by biochemistry. The expression of CD14 mRNA and protein in rat liver was measured by reverse transcriptional polymerase chain reaction and immunohistochemistry, respectively. decoction pretreatment significantly protected against acute alcohol-induced liver injury, which was evidenced by the decrease of elevated serum alanine aminotransferase and aspartate aminotransferase. In addition, the level of plasma endotoxin and up-regulation of CD14 was also suppressed by decoction in alcohol-intoxicated rats. decoction can significantly reduce CD14 expression in the lipopolysaccharide signal transduction pathway, which is one of the most important mechanisms of decoction to treat hepatic injury induced by alcohol in rats.

关键词: liver disease     alcohol     Zhihuang decoction     CD14     signal transduction    

Experimental study on the efficacy of Fuganling granula on protecting against immunological hepatic injury

Yanli LIU, Rong LIU, Cheng ZHEN, Quanfang GUO, Liping WU, Zhaoxi DING, Yushun BI, Zhiyu LIU

《医学前沿(英文)》 2009年 第3卷 第1期   页码 91-95 doi: 10.1007/s11684-009-0011-z

摘要: To study the efficacy of Fuganling granula (FGL, 复肝灵颗粒) in treating mouse immunological hepatic injury that was caused by Bacille Calmette Guerin (BCG) and lipopolysaccharide (LPS), a total of 60 mice were adopted, among which, 50 mice were given intraperitoneal injection with BCG and LPS to establish an immunological liver injury model and then were randomly divided into 5 groups (10 mice/group): 4 groups received treatment of FGL orally at the doses of 100 mg/kg (high-dosage), 50 mg/kg (middle-dosage), 25 mg/kg (low-dosage) and bifendate orally at the dose of 80 mg/kg, respectively. One group was treated with distilled water orally. The remaining 10 mice were given distilled water intraperitoneally as the normal control group. The indices of thymus, liver and spleen, and the activities of the alanine aminotransferase (ALT), aspartate aminotransferase (AST) in the serum were detected. Compared to the normal rat, the model group’s thymus index decreased significantly. The liver index and spleen index increased significantly. The activities of serum ALT and AST increased significantly (all < 0.01). Compared to the model control group, the group treated with FGL in high-dosage, middle-dosage or low-dosage can decrease the activities of ALT and AST and the group treated with FGL in high-dosage and middle-dosage can increase the thymus index significantly ( < 0.01). This experiment established the immunological liver injury model successfully and found that FGL has a remarkably protective effect on this kind of immunological hepatic injury.

关键词: Fuganling granula     immunological liver injury     bacille calmette guerin     lipopolysaccharide     mice    

标题 作者 时间 类型 操作

Protective effect of N-acetylcysteine against lipopolysaccharide injury in hepatocytes of neonatal mice

WANG Lin, LIU Yalan, XU Jianbo, TIAN Yuan, WU Heshui

期刊论文

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

期刊论文

Effect of decoction on CD14 expression in lipopolysaccharide signal transduction pathway of alcohol-induced

Rui ZHU MD , Lin SHEN MD , Jianguo LIU MD , Weili ZHANG MM , Ling YANG MD ,

期刊论文

Experimental study on the efficacy of Fuganling granula on protecting against immunological hepatic injury

Yanli LIU, Rong LIU, Cheng ZHEN, Quanfang GUO, Liping WU, Zhaoxi DING, Yushun BI, Zhiyu LIU

期刊论文