| ObjectiveTo detect the changes of Aβ1-42and Apoptosis in brain of type2diabetes mellitus (T2DM) rabbit model which have underwent the MRI scan including SWI, MRS and DTI sequences. Analyzed correlations brain pathology with MRI data in order to assess multiple model MRI ability to reflect the pathology in brain tissue and the degree of impairment with different disease duration caused by T2DM. All of the patients with T2DM accepted the Montreal of cognitive assessment (MoCA) and underwent the MRI scan including SWI, MRS and DTI sequences. Analyzed the correlation MoCA with MRI data in order to evaluate whether the multiple model MRI could detect cognitive injure at early stage. Explore the application value of SWI, MRS and DTI in detecting brain tissue pathology and cognitive injure, discuss whether SWI, MRS and DTI could play more important role in clinic early diagnosis and dynamic observation in brain injure caused by T2DM.Materials and methods1. There were18healthy rabbits divided into3groups randomly, T2DM group, High fat and high glucose group, normal control (NC) group (6rabbits each group), respectively. At first, the T2DM group rabbit were fed high fat and high glucose food for8weeks, then the rabbits were injected Alloxan (ALX)100mg/kg through the ear vein after the rabbit appeared insulin resistance (IR). Compared blood glucose and insulin values during glucose tolerance test (GTT) and the ratio of insulin0.5h (I0.5h) and glucose0.5h (G0.5h), area under the curve of insulin (AUC1), area under the curve of glucose (AUCG) and the ratio of ACU and ACUG between groups. Determine whether the T2DM rabbit model was made successfully with T2DM pathological feature by the above result.2. There were30healthy rabbits divided randomly into2groups, T2DM group (24rabbits in group) and NC group (6rabbits in group), respectively. The T2DM group were divided into4subgroups according to T2DM duration, T2DM12W group, T2DM16w group, T2DM20W group and T2DM24W group,(6rabbits each group). We detected Aβ1-42in bilateral frontal lobe, hippocampus CA3region and posterior cingulate by immunohistochemical technique and Apoptosis in hippocampus CA3region by TUNEL staining in three rabbits of group. All of the rabbits underwent MRI scan including SWI, MRS and DTI sequences. Measure the phase value of bilateral frontal lobe, hippocampus region and posterior cingulate; NAA/Cr, Cho/Cr and ml/Cr of bilateral hippocampus region; the ADC value and FA value of white matter in bilateral front lobe, anterior and posterior gyri callosus, genu of corpus callosum and splenium of corpus callosum. Analyze the correlation phase value with Aβ1-42, NAA/Cr with AI of hippocampus CA3region.3. The39patients with T2DM were divided into2subgroups according the T2DM duration:there were17patients whose T2DM duration were less10years in T2DMAgroup, there were22patients whose T2DM duration were more than or equal to10years in T2DMB group. There were28healthy volunteers who were matched with the patients with T2DM in age, gender, the education degree and blood pressure in HC group. All of the people in three groups underwent the MRI scan including T2-FLAIR, SWI, MRS and DTI sequences and assess the cognitive function with MoCA. Compared the MRI data and MoCA between groups and analyzed the correlation of MRI data with MoCA in T2DM groups.Results1. results of T2DM rabbit modelThe fasting blood sugar of rabbit in T2DM group was12.38±1.25mmol/L, which was up to diabetes mellitus (DM) diagnostic criteria. The blood sugar of T2DM rabbits in different point of time during GTT was higher than the else group (P<0.05); the fasting insulin of rabbits in T2DM group was23.23±4.65mu/L which was the highest in three groups (P<0.05). The I0.5h/G0.5h of rabbits in T2DM group was lower than the else groups (P<0.05), ACUG of rabbits in T2DM group was higher than the else groups (P<0.05), ACU1of rabbits in T2DM group was lower than the high fat and high glucose group, higher than the NC group (P<0.05), ACU1/ACUG of rabbits in T2DM group was the lowest in three groups (P<0.05)2. results of pathology and MRI in rabbit with T2DM 2.1The average optical density value of A＋1-42protein in rabbit front lobe and hippocampus CA3region in T2DM groups was higher than in NC group. There were not difference between T2DM12W group and T2DM16W group (P>0.05), the T2DM12w group and T2DM16w group were lower than T2DM20w group and T2DM24w group (P<0.05), T2DM20w group was lower than T2DM24w group (P <0.05). There were not difference in average optical density value of Aβ1-42protein in rabbit posterior cingulate between NC group, T2DM12W group and T2DM16w group (P>0.05), the T2DM20wgroup and T2DM24wgroup were higher than NC group, T2DM]2w group and T2DM16W group (P<0.05), the T2DM20wgroup was lower than T2DM24wgroup (P<0.05)2.2The AI of rabbit hippocampus CA3region in NC group was lower than all of T2DM groups (P<0.05), there were not difference between T2DM12w group and T2DM16w group (P>0.05), the T2DM20wgroup was higher than T2DM12w group and T2DM16w group (P<0.05), the T2DM24wgroup was higher than T2DM12w group,T2DM16w group and T2DM2owgroup (P<0.05)2.3The phase value of rabbit front lobe and hippocampus in NC group were higher than all of the T2DM groups (P<0.05), there were not difference between T2DM12w group and T2DM16W group (P>0.05), the T2DM2owgroup was lower than T2DM12w group and T2DM16w group (P<0.05), the T2DM24wgroup was lower than T2DM12w group,T2DM16wgroup and T2DM2owgroup (P<0.05).There were not different phase value in rabbit posterior cingulated between NC group, T2DM12w group and T2DM16w group (P>0.05), the T2DM2owgroup was lower than NC group, T2DM12w group and T2DM16w group and higher than T2DM24wgroup (P<0.05)2.4The NAA/Cr of rabbit hippocampus in NC group was1.22±0.07, higher than all of T2DM groups (P<0.05); there were not difference between T2DM12w group and T2DM16w group (P>0.05), the T2DM2owgroup was lower than T2DM12w group and T2DM16w group and higher than T2DM24wgroup (P<0.05).The Cho/Cr of rabbit hippocampus was0.50±0.01, lower T2DM groups except T2DM12w group (P<0.05); there were not difference between T2DM12w group and T2DM16wgroup (P>0.05), the T2DM2owgroup was higher than T2DM12wgroup and T2DM16W group and lower than T2DM24wgroup (P<0.05). The ml/Cr of rabbit hippocampus were not difference between NC group, T2DM12W group and T2DM16w group (P>0.05), the T2DM2owgroup was higher than NC group, T2DM12w group and T2DM16W group and lower than T2DM24wgroup (P<0.05)2.5The ADC value and FA value were not different in rabbit white matter in front lobe, anterior and posterior gyri callosus, genu of corpus callosum and splenium of corpus callosum between NC group and T2DM12W group (P>0.05);The ADC value increased and FA value decreased in posterior gyri callosus, genu of corpus callosum and splenium of corpus callosum in T2DM16wgroup compared with NC group (P<0.05), The ADC value increased and FA value decreased gradually accompany with prolonged T2DM duration in rabbit white matter in front lobe, anterior and posterior gyri callosus, genu and splenium of corpus callosum in T2DM20wgroup and T2DM24wgroup (P<0.05)2.6The correlation coefficient of average optical density value of Aβ1-42protein and phase value in front lobe, hippocampus and posterior cingulate were minus in T2DM groups (P<0.05)2.7The correlation coefficient of AI and NAA/Cr of hippocampus were minus in T2DM groups (P<0.05)3. The MoCA and MRI results of T2DM patients3.1The score of MoCA was29.39±0.83,28.29±1.86and25.54±2.15in HC group, T2DMAgroup and T2DMBgroup, respectively (P<0.05)3.2The phase value of bilateral hippocampus, front lobe and posterior cingulate in HC group were higher than T2DMAgroup and T2DMegroup (P<0.05) T2DMAgroup were higher than T2DMsgroup(P<0.05)3.3The NAA/Cr of left hippocampus in HC group was higher than T2DMAgroup and T2DMBgroup (P<0.05), Cho/Cr and Ins/Cr of left hippocampus in HC group was lower than T2DMAgroup and T2DMBgroup (P<0.05); The NAA/Cr of left hippocampus in T2DMAgroup was higher than T2DMBgroup (P<0.05), Cho/Cr and Ins/Cr of left hippocampus in T2DMAgroup was lower than T2DMBgroup (P< 0.05)3.4The ADC value in white matter in front lobe, anterior and posterior gyri callosus, genu of corpus callosum and splenium of corpus callosum in HC group were lower than T2DMAgroup and T2DMBgroup (P<0.05), T2DMAgroup were lower than T2DMBgroup (P<0.05)3.5The FA value in white matter in front lobe, anterior and posterior gyri callosus, genu of corpus callosum and splenium of corpus callosum in HC group were higher than T2DMAgroup and T2DMBgroup (P<0.05), T2DMAgroup were higher than T2DMBgroup (P<0.05)3.6The correlation coefficient of MoCA and phase value of bilateral hippocampus, front lobe and posterior cingulated in T2DMAgroup and T2DMBgroup were positive number (P<0.05); The correlation coefficient of MoCA and NAA/Cr of left hippocampus were positive number (P<0.05), The correlation coefficient of MoCA and Cho/Cr, Ins/Cr of left hippocampus were minus (P<0.05); The correlation coefficient of MoCA and ADC of measured site were minus (P<0.05) The correlation coefficient of MoCA and FA of measured site were positive number (P<0.05)Conclusion1. The T2DM rabbit model made by us was up to the DM diagnosis criteria, the T2DM rabbit model was made successfully with T2DM pathology character.2. The Aβ1-42protein deposited in rabbit front lobe, hippocampus CA3region and posterior cingulate increased gradually accompany with prolonged T2DM duration. The Aβ1-42protein deposited in front lobe, hippocampus CA3region earlier than in posterior cingulated. The Al of T2DM rabbit hippocampus was increased, the longer T2DM duration last, the more AI was detected.3. The phase value in rabbit front lobe, hippocampus CA3region and posterior cingulate decreased gradually accompany with prolonged T2DM duration. The phase value decreased in front lobe, hippocampus CA3region earlier than in posterior cingulated. The NAA/Cr decreased, Cho/Cr and ml/Cr increased in T2DM rabbit hippocampus. The changes of NAA/Cr occurred earliest and ml/Cr occurred latest among NAA/Cr, Cho/Cr and ml/Cr. The ADC value increased and FA value decreased gradually of rabbit white matter of front lobe, anterior and posterior of gyri callosus, genu of corpus callosum and splenium of corpus callosum accompany with prolonged T2DM duration. The changes of posterior gyri callosus, genu and splenium of corpus callosum occurred earlier than anterior gyri callosus and front lobe.4. The Average optical density value of Aβ1-42protein and phase value in rabbit front lobe and hippocampus CA3region in T2DM groups were negative related; The AI and NAA/Cr in rabbit hippocampus were negative related. These data implied the SWI and MRS could reflect changes of brain pathology.5. T2DM and Alzheimer’s disease (AD) had common pathology character because that Aβ1-42protein were detected in front lobe, hippocampus and posterior cingulate of T2DM rabbit.6. The patients with T2DM cognitive function were impaired heavier, the phase value of bilateral hippocampus, front lobe and posterior cingulate in T2DM patients decreased, NAA/Cr decrease, Cho/Cr and Ins/Cr increase of left hippocampus, ADC value increased and FA value decreased of white matter of front lobe, anterior and posterior of gyri callosus, genu of corpus callosum and splenium of corpus callosum, gradulally accompany with prolonged T2DM duration.7. The phase value and score of MoCA were negative related, NAA/Cr and score of MoCA were positive related, Cho/Cr, Ins/Cr and score of MoCA were negative related, ADC value and score of MoCA was negative related, FA value and score of MoCA was positive related in T2DM patients, respectively. These meaned that the multiple model of MRI could reflect the cognitive functional changes in T2DM patients.8. The SWI, MRS and DTI used together could reflect and assess brain pathology and impairment degree caused by T2DM in early stage, could estimate cognitive function impairment exactly. The multiple model MRI woule become the ideal imaging technology used in diabetic encephalopathy diagnosis in early stage, estimate impairment degree and interventions. |
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