Department of Pathology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Life Sci. 2022 Sep 15;305:120730. doi: 10.1016/j.lfs.2022.120730. Epub 2022 Jun 23.
Acute liver injury (ALI) is diagnosed by detection of elevated liver enzymes within six months after liver damage. Mesenchymal stem cells (MSCs) have recently been considered a beneficial strategy for treating various diseases due to healing secretory factors. Therapeutic effects of human umbilical cord MSCs-derived conditioned medium (hMSC-CM) were evaluated on CCl-induced ALI.
Twenty-four male Wistar rats were divided into groups including N (received saline), ALI (received CCl), RPMI (received CCl and RPMI medium), and ALI-CM (received CCl and hMSC-CM) groups. The expression of TNF-α and TGFβ-1 genes was evaluated with qPCR. Hepatic levels of TNF-α and TGF-β were measured by ELISA. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), glutathione peroxidase (GPx) activity, and catalase (CAT) activity were also assayed. Hematoxylin-eosin (H&E), Masson's trichrome, reticulin, and Periodic Acid-Schiff (PAS) stainings were conducted to evaluate tissue lesions.
CCl increased expression of TNF-α and TGF-1β at both mRNA and protein levels, while hMSC-CM decreased these parameters in the ALI-CM group. TAC levels significantly decreased in the ALI group, and CCl increased TOS and MDA levels compared with the N group. hMSC-CM treatment led to the return of these parameters to their baseline levels. GPx and CAT activity in the ALI group were significantly lower than in the N group and hMSC-CM reduced these parameters to the baseline in the ALI-CM group. hMSC-CM modulated CCl-induced tissue lesions.
The present study suggests hMSC-CM probably improves CCl-induced ALI through its antioxidant and anti-inflammatory effects.
急性肝损伤(ALI)是在肝损伤后六个月内通过检测肝酶升高来诊断的。间充质干细胞(MSCs)由于其具有愈合分泌因子的功能,最近被认为是治疗各种疾病的有益策略。本研究评估了人脐带间充质干细胞来源的条件培养基(hMSC-CM)对 CCl 诱导的 ALI 的治疗效果。
将 24 只雄性 Wistar 大鼠分为 N 组(生理盐水)、ALI 组(CCl)、RPMI 组(CCl 和 RPMI 培养基)和 ALI-CM 组(CCl 和 hMSC-CM)。通过 qPCR 评估 TNF-α和 TGFβ-1 基因的表达。通过 ELISA 测定肝组织 TNF-α和 TGF-β水平。还测定了总抗氧化能力(TAC)、总氧化状态(TOS)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GPx)活性和过氧化氢酶(CAT)活性。进行苏木精-伊红(H&E)、马松三色、网状纤维和过碘酸雪夫(PAS)染色以评估组织病变。
CCl 增加了 TNF-α和 TGF-1β 的 mRNA 和蛋白表达水平,而 hMSC-CM 在 ALI-CM 组中降低了这些参数。ALI 组的 TAC 水平显著降低,CCl 增加了 TOS 和 MDA 水平,与 N 组相比。hMSC-CM 治疗使这些参数恢复到基线水平。ALI 组的 GPx 和 CAT 活性明显低于 N 组,hMSC-CM 降低了 ALI-CM 组的这些参数至基线水平。hMSC-CM 调节 CCl 诱导的组织病变。
本研究表明,hMSC-CM 可能通过其抗氧化和抗炎作用改善 CCl 诱导的 ALI。