Gülhan Pınar Yıldız, Ekici Mehmet Savaş, Niyaz Mehmet, Gülhan Muhammet, Erçin Mustafa Emre, Ekici Aydanur, Aksoy Nurkan
Department of Chest Diseases, Düzce University School of Medicine, Düzce, Turkey.
Department of Chest Diseases, Kırıkkale University School of Medicine, Kırıkkale, Turkey.
Turk Thorac J. 2020 Jan;21(1):14-20. doi: 10.5152/TurkThoracJ.2019.180136. Epub 2020 Jan 1.
Emphysema and chronic bronchitis have different pathophysiologies but both are significant components of chronic obstructive lung disease (COPD). The levels of Matrix metalloproteinase (MMP)-9 in the bronchoalveloar lavage fluid (BALF) and in serum indicate the presence of emphysema. Intratracheal administration of elastase has been used to create a rat model of emphysema. Adipose tissue-derived mesenchymal stem cells (MSC) have been postulated to prevent or reverse emphysema, however, this has not been examined in the rat model of elastase-induced emphysema.
In this study, 31 Wistar albino rats aged 6-8 weeks and weighing 250-300 g were assessed. On day 1, the animals were treated intratracheally with 0.5 mL saline (control group, n=10), i.e., 0.5 mL saline solution containing 0.1 IU porcine pancreatic elastase (PPE) (Elastase group, n=12) or PPE plus MSC (Elastase-MSC group, n=9) was adminstered per animal. MSCs suspended in serum were injected via the caudal vein on day 21. At least 10 cells were injected. All animals were sacrificed on day 42 and the emphysema index (EI) was calculated, along with measuring the BALF and serum MMP-9 concentrations.
Porcine pancreatic elastase induced a significant degree of emphysema in the PPE groups as compared to the control group, which was determined by the EI index (p=0.008). This was not reversed by MSC treatment. The EI remained significantly low in comprison with the controls (p=0.001) and measured no different from the Elastase-treated animals. There was no statistically significant difference between the BALF and serum MMP-9 levels between the control and treatment groups.
Our findings suggest that therapeutic treatment with adipose tissue-derived MSC in rats has no effect on emphysema or on MMP9 expression, which is a known marker of emphysema.
肺气肿和慢性支气管炎具有不同的病理生理学,但二者均为慢性阻塞性肺疾病(COPD)的重要组成部分。支气管肺泡灌洗液(BALF)和血清中基质金属蛋白酶(MMP)-9的水平表明存在肺气肿。气管内注射弹性蛋白酶已被用于建立大鼠肺气肿模型。脂肪组织来源的间充质干细胞(MSC)被认为可以预防或逆转肺气肿,然而,这尚未在弹性蛋白酶诱导的肺气肿大鼠模型中得到验证。
在本研究中,评估了31只6 - 8周龄、体重250 - 300 g的Wistar白化大鼠。第1天,对动物进行气管内注射0.5 mL生理盐水(对照组,n = 10),即每只动物注射含0.1 IU猪胰弹性蛋白酶(PPE)的0.5 mL生理盐水溶液(弹性蛋白酶组,n = 12)或PPE加MSC(弹性蛋白酶 - MSC组,n = 9)。第21天,将悬浮于血清中的MSC经尾静脉注射。至少注射10个细胞。所有动物在第42天处死,计算肺气肿指数(EI),并测量BALF和血清MMP - 9浓度。
与对照组相比,猪胰弹性蛋白酶在PPE组中诱导了显著程度的肺气肿,这由EI指数确定(p = 0.008)。MSC治疗并未使其逆转。与对照组相比,EI仍显著较低(p = 0.001),且与弹性蛋白酶处理的动物相比无差异。对照组和治疗组之间的BALF和血清MMP - 9水平无统计学显著差异。
我们的研究结果表明,在大鼠中用脂肪组织来源的MSC进行治疗对肺气肿或作为肺气肿已知标志物的MMP9表达没有影响。