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Involvement of TLR4/ CXCL9/ PREX-2 pathway in the development of hepatocellular carcinoma (HCC) and the promising role of early administration of lactobacillus plantarum in Wistar rats.
Tissue & Cell ( IF 2.7 ) Pub Date : 2019-07-31 , DOI: 10.1016/j.tice.2019.07.010
Asmaa M Elshaer 1 , Omnyah A El-Kharashi 1 , Ghada Galal Hamam 2 , Enas S Nabih 3 , Yosra M Magdy 1 , Abeer A Abd El Samad 2
Affiliation  

BACKGROUND AND AIM Improvement of gut microbiota may help in preventing the progression of cirrhosis. We supposed that Lactobacillus Plantarum (L. Plantarum) protects the cirrhotic liver through suppression of TLR4/ CXCL9/ PREX-2. METHODOLOGY Rats were divided into two groups. Group I, lasts for six weeks and Group II lasts for 12 weeks. Each group was subdivided into: naïve, Lactobacillus Plantarum (L. Plantarum), thioacetamide (TAA) and TAA + L. Plantarum. Liver function tests, α fetoprotein (AFP) levels, CXCL9, PREX-2 and TLR4 expression were assessed. Histological studies were performed. RESULTS TAA induced significant deterioration in liver functions and increased AFP. There was periportal cirrhosis, vacuolated hepatocytes, decrease hepatocyte parrafin-1 (hep par-1) expression, increase proliferating cell nuclear antigen (PCNA) positive nuclei and cytokeratin AE1/AE3. The PCR results showed significant increase in TLR4, CXCL9 and PREX-2 expression. Early administration of L. Plantarum significantly decreased the expression of TLR4, CXCL9 and PREX-2 together with improvement in liver function and prevented the pathological changes. CONCLUSIONS The cirrhotic complications induced by TAA are through activation of TLR4/ CXCL9/ PREX-2 pathway and could be prevented by the early administration of L. Plantarum.

中文翻译:

TLR4 / CXCL9 / PREX-2途径参与肝细胞癌(HCC)的发展,并在Wistar大鼠中早期施用植物乳杆菌有希望的作用。

背景与目的改善肠道菌群可能有助于预防肝硬化的发展。我们认为植物乳杆菌(L. Plantarum)通过抑制TLR4 / CXCL9 / PREX-2来保护肝硬化肝。方法将大鼠分为两组。第一组持续六个星期,第二组持续12个星期。每个组再分为:原始的,植物乳杆菌(L. Plantarum),硫代乙酰胺(TAA)和TAA + L. Plantarum。评估肝功能测试,甲胎蛋白(AFP)水平,CXCL9,PREX-2和TLR4表达。进行组织学研究。结果TAA引起肝功能显着恶化和AFP升高。有门静脉周围性肝硬化,肝细胞空泡化,肝细胞parrafin-1(hep par-1)表达降低,增加增殖细胞核抗原(PCNA)阳性细胞核和细胞角蛋白AE1 / AE3。PCR结果显示TLR4,CXCL9和PREX-2表达显着增加。早期施用植物乳杆菌可显着降低TLR4,CXCL9和PREX-2的表达,并改善肝功能,并防止病理改变。结论TAA引起的肝硬化并发症是通过激活TLR4 / CXCL9 / PREX-2途径引起的,可以通过早期给予植物乳杆菌来预防。
更新日期:2019-11-01
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