The Study Of Clinical Epidemiology And The Correlate Experiment Of The Acute Cerebral Vascular Disease Inducing SIRS And MODS

The Acute Cerebral Vascular Disease (ACVD) is one of the high fatal and high mutilation diseases. In our clinical work, we found only a small part of the cases died of the primary cerebral disease such as cerebral hernia and the respiration and circulatory failure, but most of the cases could always induce Systemic Inflammatory Response Syndrome (SIRS) and Multiple Organ Dysfunction Syndrome (MODS), which is very difficult to be remedied as a clinical frequent cause of death to the ACVD patient. So the subject involves many medical science fields such as Neurology and emergency medical science. It gradually becomes a focus of several union sciences at present clinical medicine research.At present, to the epidemiologic studies, the research of the ACVD inducing SIRS and MODS in domestic and international science fields is only concentrated to the analyses about the small clinical sample, and there are few researches about the risk factor. In the empirical study, there are many researches about the pathogenesy of the initial infectious diseases (Pyemia, Necrotizing pancreatitis and etc). The reports about the pathogenesy of ACVD as a initial noninfectious diseases inducing SIRS and MODS are rare. So it is one of the most necessary to be solved at present clinical work that the epidemiology characteristic and the disease occurrence mechanism of ACVD, which is one of the several usual original noninfection inducement, inducing SIRS and MODS should be investigated as well as the question about early clinical diagnosis and prevention and treatment.ObjectiveIn this study, we use the epidemiological method to analyze the general clinical data of the patient with ACVD, and observe the regularities of the expression of not only TNF-αand IL-6, both of which are also the cytokine in serum, but also TLR-4 mRNA and CD14 mRNA on the nucleated cell in peripheral blood. The aim is to study the internal relationship between those factors and ACVD inducing SIRS/MODS by the analyses of the changing characteristic of them to discuss the possible immunological mechanism. And detect the gene expression, analysis the gene polymorphism of TRL-4 (Asp299G1y,Thr399IIe) & CD14 (-159C/T) in the peripheral blood of the patient with ACVD inducing SIRS and MODS, to reveal relationship between the susceptibility and the serious degree of this kind of disease.MethodIn this study, prospective analytical methods was adopted to analysis a larger sample including the cases of 1262 patients with ACVD in the period from Jun. 2004 to Jun. 2006, of which the documents of 153 cases of patients have been studied with following methods: 1. the method of ELASA was used to detect the expression of TNF-αand IL-6 in the patient serum of each group; 2. the method of RT-PCR was used to survey the gene expression of TLR-4 mRNA & CD14 mRNA of the nucleated cell in the peripheral blood of the ACVD patients; 3. by using the technique of PCR, and with the destination gene of TLR-4 and CD14, studied the character of gene polymorphism of the 12874th gene site-A/G (Asp299G1y), the 13174th gene site-C/T (Thr399I1e) of TRL-4 and the gene polymorphism of CD14(-159 C/T).Result1. Epidemiological Investigation: by epidemiological investigation, we have found that the incidence rate (IN) of ACVD inducing SIRS is 35.53%, and the IN of ACVD induced with MODS is 11.73%, between which there is not a significant difference; the case fatality rate (CFR) of the cerebral hemorrhage (CH) group inducing MODS is much higher than that of the cerebral infarction (CI) group inducing MODS. The first dysfunction organ is usually the lung, then the gastrointestinal tract and the kidney. We found that the age of case, focus of infection near the brain mean line, GCS, level of blood sugar, number of WBC, chronic diseases (hypertension, diabetes and etc.) is significantly different in the group comparison. They are the correlate risk factors about the ACVD inducing SIRS and MODS.2. The expression of TNF-α, IL-6 and TLR-4mRNA & CD14mRNA: (1) the expression of TNF-α, IL-6 and TLR-4mRNA & CD14mRNA in the 3rd day of disease onset all become high; (2) there are significant differences between the following each two groups, in which we can get the P<0.01, the pure ACVD group and the contrast group (CG), the group of ACVD inducing SIRS and the CG, the group of ACVD inducing MODS and the CG, the group of ACVD inducing SIRS and the pure ACVD group, the group of ACVD inducing MODS and the group of ACVD inducing SIRS, and there is a increasing tendency of the degree increase of their expression with the patient condition aggravation; (3) when the score of the patient with MODS was compared, we can get such a result that the higher the score of MODS is, the higher the expression quantity of TNF-α, IL-6, TLR-4mRNA, CD14mRNA is, and P<0.05; (4) to the patient with ACVD inducing MODS, after the comparison between the death group and the survival group, the expression of TNF-α, IL-6, TLR-4 mRNA and CD14 mRNA in the serum of the death group is notably higher than that of the survival group, and difference of the two groups is significant, P<0.01. (5) in the ACVD inducing SIRS and MODS patients, TNF-α, IL-6, TLR-4mRNA, CD14mRNA have positive correlation.3. The gene polymorphism: (1) The gene polymorphism of Asp299G1y, Thr399I1e in TLR-4: to all of the patients with ACVD and the contrast group, there is not any mutation occurring in the 12874th site A/G (Asp299G1y) and the 13174th site C/T (Thr399I1e) in TLR-4, which is seldom in Chang Chun region. (2) Gene polymorphism of CD14 promotor-159 C→T:①the TC genotype is common in the Gene polymorphism of CD14 promotor-159C→T;②about the allelic gene frequency of T/ C and the distribution of the genotypic frequency of TT,TC,CC: there are no significant differences between the pure ACVD group and the contrast group (CG), in which we can get the P>0.05; and on the contrary there are significant differences between the following each two groups in which we can get the P<0.05: they are the group of ACVD inducing SIRS and the CG, the group of ACVD inducing MODS and the CG; the MODS group of the patient score is≥9 and that of the score is<9; the death group and the survival group.Conclusion1. In the ACVD cases, there is a common probability between the two groups of CH and CI which induce SIRS and MODS. But in the MODS group, the CFR of CH is notably higher than that of CH. The case-fatality rate increases quickly with the raise of the dysfunction organ numbers, the order of the dysfunction organ is lung, gastrointestinal tract, kidney, heart and liver.2. The age of case, the pathological part near the brain mean line, GCS, the level of blood sugar, the number of WBC, the chronic diseases (hypertension, diabetes, and etc.) are the correlate risk factors about the ACVD inducing SIRS and MODS.3. There is a positive correlation between the expression content of TNF-α, IL-6, TLR-4 mRNA and CD14 mRNA in the serum of the patient with ACVD inducing SIRS and MODS and the disease condition degree, the disease progress speed, which hints the mechanism of ACVD as an original exogenous noninfectious disease inducing SIRS and MODS may be related with excessive immunologic response of the organism and detecting the content of TNF-α, IL-6 can provide to us some information about the disease condition.4. There is a close relationship between the affectability, the serious degree of the ACVD inducing SIRS/MODS and CD14 -159C/T gene polymorphism. The allele gene T is an unfavourable prognosis and high risk marker.The new idea of present study1. The subject involves Neurology and Emergency medical science and etc, deals with common issues of Acute Cerebral Vascular Disease and Multiple Organ Dysfunction Syndrome, uses theories, methods and technologies of clinical epidemiology, immunology and molecular biology, investigates MODS after cerebral original disease related problems wholly.2. Using epidemiological prospective method to large sample, after we studied the disease occurrence, disease characteristic and risk factors, we found that the correlate risk factors about the ACVD inducing SIRS and MODS were the age of patient, the pathological part near the brain mean line, GCS, the level of blood sugar, the number of WBC, the chronic diseases (hypertension, diabetes, and etc.), which could determine the disease progress and the disease turnover.3. Through the research on cytokine and expression of TLR-4 and CD14, we find that the mechanism of ACVD as an original noninfectious disease inducing SIRS and MODS is related with the excess immunologic response the organism.4. Primary discussion is about the distribution of northern population's gene polymorphism of TLR-4 and CD14, further analyses is given to the importance of gene polymorphism in ACVD inducing SIRS and MODS, the theoretic base of the clinical precognition and early treatment of SIRS and MODS are provided.