Pravastatin attenuates isoprenaline induced cardiac fibrosis in a mouse model.

IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnic & Histochemistry Pub Date : 2023-11-01 Epub Date: 2023-10-31 DOI:10.1080/10520295.2023.2260303
Abhinav Rana, Thakur Uttam Singh, Meemansha Sharma, Manju Gari, Tarun Kumar, Subhashree Parida, Madhu Cholenahalli Lingaraju, Asok Kumar Mariappan, Akhilesh Kumar, Dinesh Kumar
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Abstract

We investigated the effects of pravastatin (PRAVA) on isoprenaline (ISP) induced cardiac fibrosis using four groups of mice: untreated control, PRAVA, ISP, ISP + PRAVA groups. ISP, 20 mg/kg, was administered subcutaneously daily for 14 days. PRAVA, 20 mg/kg, was administered orally daily for 14 days. Mice were sacrificed on day15 and heart and blood samples were collected to investigate cardiac injury markers. The mean body weight for the ISP group on day 15 was decreased significantly compared to day 0; PRAVA increased the mean body weight slightly on day 15 of treatment compared to day 0. The heart:body weight ratio was increased in the ISP group compared to the control group, but the ratio was returned to near control ratio in the PRAVA + ISP group. The serum creatine kinase-myocardial band (CK-MB) level was reduced significantly in the PRAVA + ISP group compared to the ISP group. Serum triglyceride level was decreased significantly in ISP + PRAVA group compared to the ISP group. PRAVA administration significantly reduced tissue collagen I and III levels in the ISP + PRAVA group compared to the ISP group. Lipid oxidation was decreased and reduced glutathione activity was increased in the PRAVA + ISP group compared to the ISP group. IL-6, α-SMA, CTGF, TGF-β and SMAD-3 gene expressions were decreased in the PRAVA + ISP group compared to the ISP group. We found fewer inflammatory cells and less fibrosis in heart tissue in the PRAVA + ISP group compared to the ISP group. PRAVA decreased ISP induced cardiac fibrosis by reducing oxidative stress, collagen deposition and inflammation, as well as by decreasing expression of TGF-β, SMAD-3 and CTGF genes.

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普伐他汀在小鼠模型中减轻异丙肾上腺素诱导的心脏纤维化。
我们使用四组小鼠研究了普伐他汀(PRAVA)对异丙肾上腺素(ISP)诱导的心脏纤维化的影响:未经治疗的对照组、PRAVA、ISP、ISP+PRAVA组。ISP,20mg/kg,每天皮下给药14天。PRAVA,20mg/kg,每天口服给药,持续14天。在第15天处死小鼠,收集心脏和血液样本以研究心脏损伤标志物。ISP组在第15天的平均体重与第0天相比显著降低;与第0天相比,PRAVA在治疗的第15天略微增加了平均体重。与对照组相比,ISP组的心体重比有所增加,但在PRAVA+ISP组,这一比例恢复到接近对照的水平。与ISP组相比,PRAVA+ISP组的血清肌酸激酶心肌带(CK-MB)水平显著降低。与ISP组相比,ISP+PRAVA组的血清甘油三酯水平显著降低。与ISP组相比,ISP+PRAVA组的PRAVA给药显著降低了组织胶原I和III水平。与ISP组相比,PRAVA+ISP组的脂质氧化降低,还原型谷胱甘肽活性增加。与ISP组相比,PRAVA+ISP组IL-6、α-SMA、CTGF、TGF-β和SMAD-3基因表达降低。我们发现,与ISP组相比,PRAVA+ISP组的心脏组织中炎症细胞更少,纤维化更少。PRAVA通过减少氧化应激、胶原沉积和炎症,以及通过减少TGF-β、SMAD-3和CTGF基因的表达,减少ISP诱导的心脏纤维化。
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来源期刊
Biotechnic & Histochemistry
Biotechnic & Histochemistry 生物-生物工程与应用微生物
CiteScore
3.40
自引率
6.20%
发文量
46
审稿时长
6-12 weeks
期刊介绍: Biotechnic & Histochemistry (formerly Stain technology) is the official publication of the Biological Stain Commission. The journal has been in continuous publication since 1926. Biotechnic & Histochemistry is an interdisciplinary journal that embraces all aspects of techniques for visualizing biological processes and entities in cells, tissues and organisms; papers that describe experimental work that employs such investigative methods are appropriate for publication as well. Papers concerning topics as diverse as applications of histochemistry, immunohistochemistry, in situ hybridization, cytochemical probes, autoradiography, light and electron microscopy, tissue culture, in vivo and in vitro studies, image analysis, cytogenetics, automation or computerization of investigative procedures and other investigative approaches are appropriate for publication regardless of their length. Letters to the Editor and review articles concerning topics of special and current interest also are welcome.
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