The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HP...The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labeled with 131I and 125I by the Chloramine--T method and purified through Sephadex G25 column. Tewlve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5, NR ). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then fed with high cholesterol and fat diet. 125I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of 125I-SP-4 in rabbits was investigated. The uptakes (%ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macroautoradiography and microautoradiography were performed in 2 AR atheroscle-rotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. 125I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4hours postinjection were significantly higher than that of NR. The films of macroautoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of microautoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent.展开更多
Senile plaque blue autofluorescence was discovered around 40 years ago,however,its impact on Alzheimer’s disease(AD)pathology has not been fully examined.We analyzed senile plaques with immunohistochemistry and fluor...Senile plaque blue autofluorescence was discovered around 40 years ago,however,its impact on Alzheimer’s disease(AD)pathology has not been fully examined.We analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain sections and also Aβ aggregation in vitro.In DAPI or Hoechst staining,the nuclear blue fluorescence could only be correctly assigned after subtracting the blue plaque autofluorescence.The flower-like structures wrapping dense-core blue fluorescence formed by cathepsin D staining could not be considered central-nucleated neurons with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was subtracted.Both Aβ self-oligomers and Aβ/hemoglobin heterocomplexes generated blue autofluorescence.The Aβ amyloid blue autofluorescence not only labels senile plaques but also illustrates red cell aggregation,hemolysis,cerebral amyloid angiopathy,vascular plaques,vascular adhesions,and microaneurysms.In summary,we conclude that Aβ-aggregation-generated blue autofluorescence is an excellent multi-amyloidosis marker in Alzheimer’s disease.展开更多
Objective To investigate whether catalpol affects senile plaque formation and spatial learning and memory ability in the amyloid-βprotein precursor/presenilin 1(APP/PS1)double transgenic mice.
目的对所获的PS1/APP双转基因阿尔茨海默病(A lzhe im er d isease,AD)模型小鼠进行基因鉴定,进一步对其进行组织学分析,检测老年斑(sen ile p laque,SP)的形成情况。方法设计特定的引物,PCR扩增转入基因组DNA中的APP基因,对转入PS1/AP...目的对所获的PS1/APP双转基因阿尔茨海默病(A lzhe im er d isease,AD)模型小鼠进行基因鉴定,进一步对其进行组织学分析,检测老年斑(sen ile p laque,SP)的形成情况。方法设计特定的引物,PCR扩增转入基因组DNA中的APP基因,对转入PS1/APP的小鼠应用刚果红染色结合免疫组化观察Aβ沉积、小胶质细胞和星型胶质细胞的活化。结果与未转入的阴性对照相比,在PS1/APP双转基因的AD小鼠皮质和海马内可见Aβ斑块形成,围绕在Aβ斑块周围的小胶质细胞和星形胶质细胞处于活化状态,形成典型的SP结构。结论我们获得的PS1/APP双转基因小鼠能够模拟AD患者脑内的主要病理过程,提供有效的实验动物模型。展开更多
基金Supported by grants from the Ministry of Health of China, No. 96-1-148
文摘The clinical prospect of radioiodinated SP-4 as an atherosclerotic plaque imaging agent was studied. The SP-4 was synthesized by a solid phase method and identified by an amino acid analysis after purification with HPLC. SP-4 was labeled with 131I and 125I by the Chloramine--T method and purified through Sephadex G25 column. Tewlve New Zealand rabbits were divided into an atherosclerotic group (n = 7, AR) and a control group (n = 5, NR ). All of the atherosclerotic rabbits were intravenous administrated with bovine serum albumin, then fed with high cholesterol and fat diet. 125I-SP-4 was intravenous administrated to the rabbits of both groups. The biodistribution of 125I-SP-4 in rabbits was investigated. The uptakes (%ID/g) in blood and thoracic aorta and abdominal aorta were calculated 4 hours postinjection. Macroautoradiography and microautoradiography were performed in 2 AR atheroscle-rotic abdominal aortas. The clearance of radioactivity from plasma was very rapid. 125I-SP-4 was mainly excreted through kidneys. The radioactive uptakes of abdominal aorta and thoracic aorta of AR at 4hours postinjection were significantly higher than that of NR. The films of macroautoradiography showed focal accumulation of the radioactivity in the areas of a newly formed edges of atherosclerotic plaques. On the slices of microautoradiography, the obvious radioactive accumulation could be found in the atherosclerotic plaques. Thus it was seen that the SP-4 remained its biological activity after radioiodination and was located at atherosclerotic lesions, it is potentially useful as an atherosclerotic plaque imaging agent.
基金supported by the National Natural Science Foundation of China(81472235)the Shanghai Jiao Tong University Medical and Engineering Project(YG2021QN53,YG2017MS71)+1 种基金the International Cooperation Project of National Natural Science Foundation of China(82020108017)the Innovation Group Project of National Natural Science Foundation of China(81921002).
文摘Senile plaque blue autofluorescence was discovered around 40 years ago,however,its impact on Alzheimer’s disease(AD)pathology has not been fully examined.We analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain sections and also Aβ aggregation in vitro.In DAPI or Hoechst staining,the nuclear blue fluorescence could only be correctly assigned after subtracting the blue plaque autofluorescence.The flower-like structures wrapping dense-core blue fluorescence formed by cathepsin D staining could not be considered central-nucleated neurons with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was subtracted.Both Aβ self-oligomers and Aβ/hemoglobin heterocomplexes generated blue autofluorescence.The Aβ amyloid blue autofluorescence not only labels senile plaques but also illustrates red cell aggregation,hemolysis,cerebral amyloid angiopathy,vascular plaques,vascular adhesions,and microaneurysms.In summary,we conclude that Aβ-aggregation-generated blue autofluorescence is an excellent multi-amyloidosis marker in Alzheimer’s disease.
文摘Objective To investigate whether catalpol affects senile plaque formation and spatial learning and memory ability in the amyloid-βprotein precursor/presenilin 1(APP/PS1)double transgenic mice.
文摘目的对所获的PS1/APP双转基因阿尔茨海默病(A lzhe im er d isease,AD)模型小鼠进行基因鉴定,进一步对其进行组织学分析,检测老年斑(sen ile p laque,SP)的形成情况。方法设计特定的引物,PCR扩增转入基因组DNA中的APP基因,对转入PS1/APP的小鼠应用刚果红染色结合免疫组化观察Aβ沉积、小胶质细胞和星型胶质细胞的活化。结果与未转入的阴性对照相比,在PS1/APP双转基因的AD小鼠皮质和海马内可见Aβ斑块形成,围绕在Aβ斑块周围的小胶质细胞和星形胶质细胞处于活化状态,形成典型的SP结构。结论我们获得的PS1/APP双转基因小鼠能够模拟AD患者脑内的主要病理过程,提供有效的实验动物模型。
