Human Anatomy & Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Medical Biochemistry and Molecular Biology Department, Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Algomhoria Street, Mansoura, 35516, Egypt.
BMC Gastroenterol. 2023 Sep 21;23(1):323. doi: 10.1186/s12876-023-02932-y.
One of the most frequent disorders is liver fibrosis. An improved understanding of the different events during the process of liver fibrosis & its reversibility could be helpful in its staging and in finding potential therapeutic agents.
The goal of this research was to evaluate the relationship among CD34 + HPSCs, SDF-1α, and CXCR4 receptor expression with the percentage of the area of hepatic fibrosis.
Thirty-six male Sprague-Dawley rats were separated into the control group, liver injury group & spontaneous reversion group. The liver injury was induced by using 2 ml/kg CCl4 twice a week. Flow cytometric examination of CD34 + cells in the blood & liver was performed. Bone marrow & liver samples were taken for evaluation of the SDF-1α mRNA by PCR. Liver specimens were stained for histopathological and CXCR4 immuno-expression evaluation.
In the liver injury group, the hepatic enzymes, fibrosis area percentage, CXCR4 receptor expression in the liver, CD34 + cells in the blood and bone marrow & the level SDF-1α in the liver and its concentration gradient were statistically significantly elevated with the progression of the liver fibrosis. On the contrary, SDF-1α in the bone marrow was statistically significantly reduced with the development of liver fibrosis. During the spontaneous reversion group, all the studied parameters apart from SDF-1α in the bone marrow were statistically substantially decreased compared with the liver injury group. We found a statistically substantial positive correlation between fibrosis area and all of the following: liver enzymes, CXCR4 receptor expression in the liver, CD34 + cells in the blood and liver, and SDF- 1α in the liver and its concentration gradient. In conclusion, in CCl4 rat model, the fibrosis area is significantly correlated with many parameters in the blood, bone marrow, and liver, which can be used during the process of follow-up during the therapeutic interventions.
肝脏纤维化是最常见的疾病之一。深入了解肝脏纤维化过程中的不同事件及其逆转的可能性,有助于对其进行分期,并寻找潜在的治疗药物。
本研究旨在评估 CD34+HPSCs、SDF-1α 和 CXCR4 受体表达与肝纤维化面积百分比之间的关系。
将 36 只雄性 Sprague-Dawley 大鼠分为对照组、肝损伤组和自发逆转组。每周两次用 2ml/kg 的 CCl4 诱导肝损伤。采用流式细胞术检测血液和肝脏中 CD34+HPSCs 的表达。提取骨髓和肝脏样本,通过 PCR 检测 SDF-1αmRNA 的表达。对肝组织进行染色,评估 CXCR4 免疫表达。
在肝损伤组中,肝酶、纤维化面积百分比、肝内 CXCR4 受体表达、骨髓和血液中 CD34+HPSCs 以及肝内 SDF-1α 及其浓度梯度均随肝纤维化的进展而显著升高。相反,随着肝纤维化的发展,骨髓中的 SDF-1α 显著降低。在自发逆转组中,除骨髓中 SDF-1α 外,所有研究参数均显著低于肝损伤组。我们发现纤维化面积与以下所有参数之间存在显著的正相关:肝酶、肝内 CXCR4 受体表达、骨髓和血液中的 CD34+HPSCs 以及肝内 SDF-1α 及其浓度梯度。结论:在 CCl4 大鼠模型中,纤维化面积与血液、骨髓和肝脏中的许多参数显著相关,可在治疗干预过程中进行随访。