Dynamic Changes In Plasma Mitochondrial DNA Concentration In Patients With Early Severe Acute Pancreatitis

Objectives:The main purposes of this study were to investigate the dynamic changes of plasma mitochondrial deoxynucleotide（mtDNA）levels in patients with severe acute pancreatitis（SAP）at early stage,and to study the consistency and correlation between the plasma mtDNA concentration and the progression of SAP disease.Methods:In this study,the whole of SAP patients admitted to the intensive care unit（ICU）of our hospital were continuously included as the research objects.Then,the venous blood samples from the research objects were collected respectively in the four time points of day 1,3,5and 7.Through laboratory determination,the plasma concentration of mtDNA and some related clinical inspection index were measured.At the same time,the basic characteristic data,relevant clinical test indicators and commonly used assessment system scores in SAP disease.The Kruskal Wallies test was used to analyze whether there exist statistical difference in the trend of plasma mtDNA levels in several time,etiologies and underlying diseases.In order to determine whether there were statistical differences in plasma mtDNA concentrations among SAP patients of different ages and gender groups,the Mann-Whitney U test was adopted.Furthermore,for the sake of determining whether there is consistency or correlation statistical significance among the dynamic concentration change trends of mtDNA,clinical laboratory tests and scoring system evaluation data,we adopted the two-way analysis of variance or Spearman’s correlation coefficient statistical analysis method.P<0.05 was considered to be statistically significant.Results:The plasma mtDNA concentration of the patients with SAP was significantly higher than that in healthy controls（9.85[IQR 6.87-12.85]vs.1.24[IQR 1.12-1.43]ng/ml,Z=-5.20,P<0.05）.The mtDNA levels increased rapidly,peaking on day 3（13.49[IQR 10.77 16.03]ng/ml）after admission（8.81[IQR 6.00 11.12]ng/ml）,and began to decrease on day5（10.20[IQR 6.67 12.12]ng/ml）and days 7（8.43[IQR 6.03 9.84]ng/ml）（χ²=26.75,P<0.05）.The trend remained statistically consistent among APACHE Ⅱ score,SOFA score,CRP and mtDNA levels（F=26.40,P<0.05;F=23.49,P<0.05;F=6.61,P<0.05）.Contrastingly,the consistency analysis of trends in PCT,Ca²⁺and mtDNA concentrations showed no statistical significance（F=2.68,P>0.05;F=1.13,P>0.05）.In the correlation among mtDNA level,APACHE Ⅱ score,SOFA score and Ranson score was statistically significant（R=0.39,P<0.05;R=0.27,P<0.05;R=0.76,P<0.05）.However,there did not exist significant correlation with CRP,PCT and Ca²⁺concentrations（R=0.11,P>0.05;R=-0.13,P>0.05;R=0.12,P>0.05）.Interestingly,plasma mtDNA levels in the elderly or women with SAP were significantly higher than those in youth or men（Z=-2.28,P<0.05;Z=-2.29,P<0.05）.However,there was no statistically significant difference in plasma mtDNA levels among different etiology,BMI,disease time and basic diseases groups（F=1.43,P>0.05;F=1.85,P>0.05;F=0.39,P>0.05;F=0.41,P>0.05）.Conclusions:（1）The concentration of plasma mtDNA was significantly increasing in SAP patients compared with healthy adult controls.In compared with the patient on the day 1 of admission,plasma mtDNA concentration began to rise sharply and reached the peak on the day 3.It began to decline on the day 5 and day 7.（2）The change trend among APACHE Ⅱ score,SOFA score,CRP level and mtDNA concentration had statistical significance.However,the alters of plasma PCT,Ca²⁺and mtDNA concentrations showed no statistically significant trends.The APACHE Ⅱ score,SOFA score and Ranson score were statistically correlated with mtDNA level,while the plasma CRP,PCT and Ca²⁺concentrations were not significantly correlated with mtDNA concentration.（3）Compared with the non-elderly group,plasma mtDNA concentration of SAP patients in the elderly group was significantly higher.Plasma mtDNA levels were significantly higher in female patients than those in male patients.However,there was no statistically significant difference in plasma mtDNA concentration among SAP patients with different etiology,underlying diseases,disease times,and BMI.（4）The plasma mtDNA levels were significantly elevated in SAP patients,and maintained slickly consistency and correlation with clinical laboratory indicators,some disease assessment system data.As a consequence,it can be used as a biomarker for early prediction and monitoring of the SAP disease progresses and changes.