Lin Hai-Yan, Xu Lei, Xie Shuan-Shuan, Yu Fei, Hu Hai-Yang, Song Xiao-Lian, Wang Chang-Hui
Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University Shanghai 200072, Peoples PR China ; Department of Respiratory Medicine, Huai'an First Peoples's Hospital, Nanjing Medical University Nanjing, China.
Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University Shanghai 200072, Peoples PR China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):8958-67. eCollection 2015.
Mesenchymal stem cells (MSCs) came out to attract wide attention and had become one of the hotspots of most diseases' research in decades. But at present, the mechanisms of how MSCs work on chronic asthma remain undefined. Our study aims at verifying whether MSCs play a role in preventing inflammation and airway remodeling via PI3K/AKT signaling pathway in the chronic asthma rats model.
First, an ovalbumin (OVA)-induced asthma model was built. MSCs were administered to ovalbumin-induced asthma rats. The total cells in a bronchial alveolar lavage fluid (BALF) and inflammatory mediators in BALF and serum were measured. Histological examination of lung tissue was performed to estimate the pathological changes. Additionally, the expression of phosphorylated-Akt (p-Akt) in all groups was measured by western blot and immunohistochemistry (IHC).
Compared to normal control group, the degree of airway inflammation and airway remodeling was significantly increased in asthma group. On the contrary, they were obviously inhibited in MSCs transplantation group. Moreover, the expression of p-Akt was increased in lung tissues of asthmatic rats, and suppressed by MSCs transplantation.
Our results demonstrated that MSCs transplantation could suppress lung inflammation and airway remodeling via PI3K/Akt signaling pathway in rat asthma model.
间充质干细胞(MSCs)已引起广泛关注,并在数十年间成为大多数疾病研究的热点之一。但目前,MSCs在慢性哮喘中发挥作用的机制仍不明确。我们的研究旨在验证在慢性哮喘大鼠模型中,MSCs是否通过PI3K/AKT信号通路在预防炎症和气道重塑中发挥作用。
首先,建立卵清蛋白(OVA)诱导的哮喘模型。将MSCs给予卵清蛋白诱导的哮喘大鼠。检测支气管肺泡灌洗液(BALF)中的总细胞数以及BALF和血清中的炎症介质。对肺组织进行组织学检查以评估病理变化。此外,通过蛋白质免疫印迹法和免疫组织化学(IHC)检测所有组中磷酸化Akt(p-Akt)的表达。
与正常对照组相比,哮喘组气道炎症和气道重塑程度显著增加。相反,在MSCs移植组中它们明显受到抑制。此外,哮喘大鼠肺组织中p-Akt的表达增加,而MSCs移植可抑制其表达。
我们的结果表明,在大鼠哮喘模型中,MSCs移植可通过PI3K/Akt信号通路抑制肺部炎症和气道重塑。