RESUMO
【Objective】 To explore the risk of Alzheimer′s disease (AD) transmitted by blood transfusion. 【Methods】 There were 10 APP/PS1 mice of 3, 6 and 9 months old, half female and half male, and the cognitive and behavioral abilities of C57 mice of the same age were measured, and the blood of the oldest APP/PS1 mice with no behavioral changes were collected to detect the contents of Aβ40 and Aβ42. The polymers Aβ40 and Aβ42 were prepared and Western blotting analysis was conducted. Kunming mice aged from 6 to 7 months were randomly divided into 6 groups (10 mice/ group, half male and half female). The blood of APP/PS1 mice was injected intravenously in experimental group 1-2(100 μL/mouse) with high frequency injection (3 times/week) and low frequency injection (1 time/week), respectively. In experimental group 3-4, Aβ40 and Aβ42 polymerized mixture (100 μL/mouse) were injected in high frequency and low frequency, respectively. The control group 1-2 was injected with the same amount of normal saline, with high frequency and low frequency, respectively. The above groups were injected for 4 weeks, and the cognitive and behavioral abilities were tested and analyzed one week after injection. Finally, the contents of Aβ40 and Aβ42 in blood of Kunming mice were detected. 【Results】 Change in cognitive and behavioral ability showed in 9 months old APP/PS1 mice, but not in 3 and 6 months old APP/PS1 mice. The contents of Aβ40 and Aβ42 (pg/mL) in blood of 6-7 months old APP/PS1 mice were 418.40±2.18 and 15.68±0.20, respectively. Except for monomers, most of the polymerized mixtures of Aβ40 and Aβ42 were dimers and trimers. In both high frequency and low frequency, Kunming mice transfused with blood of APP/PS1 mice (experimental group 1-2) showed a certain degree of anxiety-like behavior and short-term memory shortening in open-field test and conditioned fear test, but without significant difference. There was no significant difference in open field test, new object recognition, Barnes maze and cognitive behavior analysis of conditioned fear between experimental group 3-4 and the control group. The levels of blood Aβ40 and Aβ42(pg/mL) of Kunming mice detected by ELISA were 10.30±0.08 and 3.360±0.005, respectively, and there was no significant difference between the two groups. 【Conclusion】 Blood transfusion of APP/PS1 mice and the mixture of Aβ40 and Aβ42 have no significant effect on the cognitive function of healthy Kunming mice in a short time, and the risk of AD transmission is relatively low.
RESUMO
【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.
RESUMO
【Objective】 To investigate the effect of intravenous immunoglobulin(IVIG) with different Aβ antibody content on the cognitive function of Alzheimer′s disease model mice. 【Methods】 IVIG from 8 domestic blood products companies were selected. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of Aβ40/42 antibody. Three kinds of IVIG with high, middle and low Aβ42/40 antibody levels were selected to treat 3xTg-AD mice. Forty 3-month-old 3xTg-AD mice were randomly divided into 4 groups with 10 mice in each group(half male and half female). Three treat groups were intraperitoneally injected with three kinds of IVIG with 1g·kg-1 for 12 weeks(twice a week). The controls were injected with the same volume of saline. Behavioral tests were performed immediately by using the mouse behavior analysis system after a total of 24 injections. 【Results】 The concentrations of antibodies(μg/mL) against Aβ40 monomer in IVIG ranged 0.7±0.05 to 3.1±0.05, concentrations of antibodies against Aβ40 oligomer ranged 11.7±0.7 to 32.0±2.2, concentrations of antibodies against Aβ42 monomer ranged 1.8±0.1 to 27.9±0.3, and concentrations of antibodies against Aβ42 oligomeric ranged 2.3±0.1 to 49.4±2. High(IVIG-1), medium(IVIG-8) and low(IVIG-6) IVIG were selected for mice study. In the open field test, the time of four groups of mice entering the central area(s) was 0.5±0.9, 23.4±6.1(P<0.0001), 4.6±2.8 and 2.6±2.3, respectively; the number of feces(grains) was 1.6±0.7(P<0.0001), 1.2±0.4(P<0.0001), 2.4±0.5(P<0.001) and 3.8±0.8, respectively. In the novel object recognition test, the scores of exploring new objects were 71.3±29.5(P<0.05), 71.8±20.5(P<0.05), 75.9±26.9(P<0.01) and 25.6±23.7, respectively. In the Barnes maze test, the time of exploring the target hole in the IVIG-8 group was significantly longer than that in the control on the 6th day(50.3±19.3 vs 21±14.6, P<0.05) and the 13th day(58.2±20.9 vs 19.2±15.9, P<0.005), but there was no significant difference between the IVIG-1, 6 groups and the control. 【Conclusion】 There is a significant difference in the level of Aβ40/42 antibody among 8 kinds of domestic IVIG. Domestic IVIG could improve the cognitive function of 3-month-old 3xTg-AD mice after continuous intervention for 3 months. The improvement effect, however, was related to the Aβ antibody in IVIG, but not to the antibody concentration.