RELATIONSHIP BETWEEN MIR-21 EXPRESSION IN SERUM AND INFLAMMATORY CHANGES AND PROGNOSIS IN SEPTIC RATS

Yan Zhao*, Yadong Yu**, Xia Li***, #

*Department of Emergency, The Affiliated Hospital of Bengbu Medical College & Lianyungang Second People’s Hospital & Lianyungang Cancer Hospital - **Department of Emergency, Lian Shui People's Hospital, NO.6 RedSun East Road, Lianshui, Jiangsu, 223400, China - ***Department of Geriatric, Huai’an Hospital Affiliated to Xuzhou Medical University & Huai’an Second People’s Hospital, 62 Huaihai Road South, Huai’ an 223002, P.R. China

Objective: To study the relationship between miR-21 expression in serum and inflammatory changes and prognosis in septic rats. 

Methods: A rat sepsis model was established by Cecal Ligation and Puncture (CLP). Forty healthy male SD rats were randomly divided into four groups: a control group (sham operation group, n=10) and an experimental group (n=30), which was further divided into three groups (CLP operation group, n=10) according to different blood sampling times at 6h, 12h and 24h after operation. Differently expressed miRNAs in the serum of the control group and rats at 24 hours after CLP operation were screened by fluorogenic quantitative PCR (qPCR). Levels of miR-21 and inflammatory factors (TNF-α, IL-1 and IL-6) in rat serum were detected at different time points. The correlation between miR-21 and inflammatory factors was analysed by Spearman correlation, while changes in blood routine indicators in rats with sepsis at various time points were tested. Lastly, the survival curve of septic rats was drawn using the Kaplan-Meier curve. 

Results: Compared with the control group, the expression levels of miR-155 and miR-21 were significantly increased, and miR-21 was the miRNA with the highest fold difference. The level of miR-21 and inflammatory factors (TNF-α, IL-1 and IL-6) in the sepsis group was significantly higher than that in the control group (P<0.01), and both were concentration dependent (P<0.05). Correlation analysis indicated that miR-21 expression level and inflammatory factors TNF-α, IL-6, and IL-1 were positively correlated, while organ function damage indicators such as urea nitrogen, creatinine, alanine aminotransferase, creatine kinase and high mobility group protein 1 (HMGB1) were significantly higher than the control group (P<0.05). Furthermore, the platelet count was significantly decreased (P<0.05). The Kaplan-Meier survival curve suggested that the death rate was the fastest in the 12h to 24h after CLP surgery in rats, and the survival rate was 25% during the 42h period, which was only 18% at 72 hours. 

Conclusion: The level of miR-21 and inflammatory factors (TNF-α, IL-1 and IL-6) in septic rats’ serum are significantly up-regulated and are associated with poor prognosis in rats. Thus, miR-21 may be involved in the occurrence and development of sepsis.