Department of clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Tissue Cell. 2019 Oct;60:38-47. doi: 10.1016/j.tice.2019.07.010. Epub 2019 Jul 31.
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.
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.
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.
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.
改善肠道微生物群可能有助于预防肝硬化的进展。我们假设植物乳杆菌（L. Plantarum）通过抑制 TLR4/CXCL9/PREX-2 来保护肝硬化肝脏。
大鼠分为两组。第 I 组持续 6 周，第 II 组持续 12 周。每组又分为：天真组、植物乳杆菌（L. Plantarum）组、硫代乙酰胺（TAA）组和 TAA+L. Plantarum 组。评估肝功能试验、α胎蛋白（AFP）水平、CXCL9、PREX-2 和 TLR4 的表达。进行组织学研究。
TAA 导致肝功能显著恶化并增加 AFP。存在门管区周围肝硬化、空泡化肝细胞、肝石蜡-1（hep par-1）表达减少、增殖细胞核抗原（PCNA）阳性核和细胞角蛋白 AE1/AE3 增加。PCR 结果显示 TLR4、CXCL9 和 PREX-2 的表达显著增加。早期给予植物乳杆菌可显著降低 TLR4、CXCL9 和 PREX-2 的表达，改善肝功能，预防病理变化。
TAA 诱导的肝硬化并发症是通过 TLR4/CXCL9/PREX-2 途径激活引起的，可以通过早期给予植物乳杆菌来预防。
