Relationship Between Plasma Aβ42 And T-tau Proteins And Cerebral Injury After Cardiopulmonary Bypass In Elderly

Objectives: To investigate the clinical value of plasma Aβ42, t-tau protein in diagnosis of cerebral injury after the hypothermic cardiopulmonary bypass(CPB), we established piglet model to observe the perioperative changes of the proteins. To confirm the results of animal experiments, a clinical trial are operated, in which we observed the perioperative changes of the plasma Aβ42, t-tau protein in patients undergoing the CPB.Methods:1. A piglet model of cerebral injury after CPB on 24 Bama pigs was established by simulated environment and method of clinical operation. MRI proceeded before and after CPB, HE and Nissl staining after execution were used to assess modeling results. The value of diffusion-weighted imaging(DWI) in diagnosis of CPB postoperative brain damage was used by consistency analysis.2. Plasma of 20 piglets, which were divided into experimental group(CPB group,10 pigs) and control group(sham group, 10 pigs) randomly, was extracted before and after the surgeries for enzyme linked immunosorbent assay(Elisa) of Aβ42 and t-tau protein. DWI examinations confirmed that there are brain damages with the CPB group and without the sham group. Cognitive function of the pigs after CPB was evaluated by improved color memory experiment. Correlation between plasma Aβ42or t-tau protein and improved color memory experiment score was observed by multilevel linear model.3. Tissues of injured region after CPB were proceeded Td T-mediated d UTP nick end labeling(Tunel) for cell apoptosis detection. Expressions of Caspase 3, Caspase 8,bcl-2 and bax proteins were observed using by immunohistochemistry for investingating the possible apoptosis mechanisms.4. 60 olderly patients(≥60 y), who were hospitalized in the Cardiovascular Surgery of Fujian Provincial Hospital between March 2012-March 2014, voluntarily,were divided into experimental group and control group according to the score ofmontreal cognitive assessment(Mo Ca) 24 h after CPB. Plasma was extracted before and after the surgeries for Elisa of Aβ42 and t-tau protein. Correlation between plasma Aβ42 or t-tau protein and Mo Ca score was observed by multilevel linear model.Results:1. The piglet model of cerebral injury after CPB was established successfully.Ischemic necrosis in brain tissues could be observed in imaging, while necrosis and nerve cell changes in pathology. Results of DWI were consistent with the pathological findings. And the DWI was more sensitive than T1 WI, T2 WI.2. In animal experiments,Protein levels of plasma Aβ42, t-tau at 1 d after CPB were increased significantly compared with preoperative levels and has significant difference compared with control group(P<0.05). Level of the Aβ42 protein tended to decreased at 3 d after CPB and reduced under the preoperative at 7 d. But t-tau protein sustained high levels. The improved color memory experiment scores of pigs at 1d after CPB, which were significantly lower than control group, could gradually return to the preoperative level at 7 d. The Aβ42 protein had no effects on the improved color memory test score(P>0.05), and t-tau protein had significantly effect(P<0.05).3. A large number of cell apoptosis could be observed in injured brain tissues after CPB in tunnel. And apoptosis at 24 h after CPB was more significant than 6 h.Expressions of Caspase 3, Caspase 8, bcl-2 and bax proteins were widespread in the injured brain tissues. Caspase 3, Caspase 8 and bax proteins overexpressed in injured brain after CPB(P<0.05), while bcl-2 did not(P>0.05).4. The MoCa scores of pateints in experimental group could increase at 1 w after CPB but still under preoperative level. Protein levels of plasma Aβ42, t-tau at 24 h after CPB were increased significantly compared with preoperative levels and has significant difference compared with control group(P<0.05). Aβ42 protein level at 1w was lower than preoperative level. But t-tau protein sustained high levels. Both of Aβ42 and t-tau protein had significantly effect to Mo Ca scores(P<0.05).Conclusions:1. The piglet model we established can be used to study cerebral injury after CPB.2. DWI is more sensitive than MRI and more suitable on the early diagnosis of brain damage after CPB.3. Brain nerve cells produce apoptosis through mitochondria signaling pathway and death receptor signaling pathway receptors.4. Plasma Aβ42, t-tau protein levels after CPB can be used to indicate the evaluation of cognitive dysfunction.