The Association And Pathogenesis Study Of Mycoplasma Pneumoniae And Kawasaki Disease

PurposeKawasaki disease(KD),namely mucocutaneous lymph node syndrome,is an acute febrile rash vasculitis disease in children,which usually occurs in children under 5 years old.Its pathological feature is systemic small and medium vasculitis,which mainly involves the coronary arteries,leading to coronary Coronary artery disease such as arterial dilation or coronary artery aneurysm,is one of the risk factors for acquired heart disease for children in adulthood.The epidemiological investigation of KD believes that infectious factors may be one of the causes of KD,and reports have found that Mycoplasma pneumoniae(MP)infection may be related to KD.Therefore,this study aims to investigate the relationship between MP and KD,and to explore the possible pathogenesis.Method1.Relationship between MP infection and KD:Include children diagnosed with KD in Fujian Provincial Maternity and Child Health Hospital from January 2015 to December 2018,and divide them into MP-infected KD group and non-MP-infected KD group,and extract general medical records and clinical manifestations,Laboratory indicators,echocardiographic results,descriptive analysis of data using IBM SPSS,measurement data using t-test or rank sum test,count data usingχ~2test for single factor analysis,and logistic regression analysis for statistically significant data.2.In vitro experiments to explore the pathogenesis of KD caused by MP:(1)Inflammation index detection:HCAEC were treated with different concentrations of Mp-LAMPs,the expression levels of intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),tumor necrosis factor-α(TNF-ɑ),interleukin-6(IL-6),lactic acid dehydrogenase(LDH),inducible nitric oxide synthase(i NOS)in each group of cells were detected by Western Blot,RT-PCR and ELISA;(2)Detection of mitochondrial function and autophagy in cultured cells in vitro:treat HCAEC with different concentrations of Mp-LAMPs,Carbonyl cyanide m-chlorophenyl hydrazone(CCCP),Cyclosporin A(Cs A),Mp-LAMPs+CCCP and Mp-LAMPs+Cs A,and observe the mitochondrial structure,mitochondrial membrane potential and reactive oxygen species(ROS)content changes through a fluorescence microscope,and detect the content changes of adenosine triphosphate(ATP)and the levels of mitochondrial autophagy-related signal,such as phosphatase and tensin homologue-induced putative kinase 1(PINK1),Parkin,P62,LC3.Result1.330 children with KD were enrolled in this study,including 159children with MP-infected and 171 children with non-MP-infected.There was a significant difference in the age(1.57 years VS 1.42 years,P=0.000),the proportion of children with fever>10 days(27.0%VS 16.4%,P=0.034),blood sodium(134.38mmol/L VS 135.71mmol/L,P=0.019),albumin(35.90g/L VS36.91g/L,P=0.042),prealbumin(11.43mg/d L VS 12.73mg/d L,P=0.025),and incidence of small coronary aneurysms(57.8%VS 69.0%,P=0.035)of the two groups of children;Logistic regression analysis showed that MP infection(OR:0.515;95%CI:0.309-0.860;P=0.011),serum sodium(OR:0.910;95%CI:0.851-0.972;P=0.005)and prealbumin(OR:0.900;95%CI:0.854-0.949;P≤0.001)are variables related to KD small coronary aneurysms.2.In HCAEC,compared with the blank control group(without special intervention),the expressions of ICAM-1,VCAM-1,i NOS,TNF-ɑ,IL-6 and LDH in the Mp-LAMPs treatment group were increased and is concentration-dependent.3.In HCAEC,compared with the blank control group(without special intervention),it was found that the mitochondrial membrane potential decreased,ATP content decreased,ROS accumulation and mitochondrial autophagy enhanced in the Mp-LAMPs treatment group,and CCCP played a promoting role,while Cs A played a suppressing role.4.In HCAEC,compared with the blank control group(without special intervention),the expression of PINK1,Parkin and LC3 in the Mp-LAMPs treatment group was up-regulated,while the expression of P62 was down-regulated.Conclusion1.There is a certain correlation between MP infection and KD.KD children with MP infection are older,have a longer fever and lower serum sodium,albumin and prealbumin levels.MP infection,serum sodium and prealbumin levels are variables associated with KD small coronary aneurysms.2.In HCAEC,Mp-LAMPs can induce mitochondrial autophagy mediated by the PINK1/Parkin pathway,up-regulate the expression of LC3,and down-regulate the expression of P62,synergizeing oxidative stress,promoting inflammation,promoting the release of inflammatory mediators such as TNF-ɑ,IL-6,ICAM-1,VCAM-1 and LDH,which leads to inflammatory infiltration of HCAEC,in turn causes coronary artery lesion.