高血压脑出血患者β淀粉样蛋白的表达及其与血肿周围组织细胞凋亡的关系
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摘要
目的探讨高血压脑出血(HICH)患者β淀粉样蛋白(Aβ)的表达及其与血肿周围组织细胞凋亡的关系。方法收集2010年3月到2016年3月该院收治的42例拟行颅脑血肿清除术的HICH患者。根据发病到接受手术的时间,将42例患者分为A组(<6h,20例)、B组(6～<12h,9例)、C组(12～<24h,6例)、D组(24～48h,4例)和E组(>48h,3例)。以血肿周围组织为研究标本,以远离血肿脑组织为对照标本。分别予以HE染色,DNA断裂的原位末端标记法(TUNEL法)检测各组血肿周围组织凋亡细胞。采用酶联免疫吸附试验和免疫组化法检测各组血清和血肿周围组织Aβ的表达。结果与对照标本比较,A、B、C、D、E组血肿周围组织凋亡细胞个数均增多(P<0.05);与A组比较,B、C、D、E组血肿周围组织凋亡细胞个数均增多(P<0.05),且随着HICH发病时间到接受手术时间的延长,血肿周围组织凋亡细胞个数呈先增多后减少,以24～48h血肿周围组织凋亡细胞个数最多;与A组比较,B、C、D、E组血清Aβ的表达均升高(P<0.05),血肿周围组织Aβ阳性细胞个数均增多(P<0.05),且随着HICH发病时间到接受手术时间的延长,血清和血肿周围组织Aβ的表达呈先升高后下降,以12～<24h血清和血肿周围组织Aβ的表达最高;与对照标本比较,A、B、C、D、E组血肿周围组织Aβ阳性细胞个数均增多(P<0.05);Pearson相关分析,血清Aβ含量和血肿周围组织凋亡细胞个数之间呈正相关(r=0.482,P=0.001),血肿周围组织Aβ阳性细胞个数和血肿周围组织凋亡细胞个数之间呈正相关(r=0.940,P<0.05)。结论 HICH患者血肿周围组织中存在着大量凋亡细胞,HICH血清和血肿周围组织存在Aβ高表达。血清Aβ含量、血肿周围组织Aβ阳性细胞数目与血肿周围组织凋亡细胞数目呈正相关,提示Aβ可能参与HICH血肿周围组织细胞凋亡。
Objective To explore the expression of amyloidβ(Aβ)in patients with hypertensive intracerebral hemorrhage(HICH)and its relationship with apoptosis of perihematomal tissue.Methods 42 HICH patients who underwent brain hematoma removal in the hospital from June 2010 to March 2016 were enrolled in the study.According to the time of onset to surgery,42 HICH patients were divided into A group(<6 h,20 cases),B group(6-<12 h,9 cases),C group(12-<24 h,6 cases),D group(24-48 h,4 cases)and E group(>48 h,3 cases).The perihematomal tissue was taken as the research sample and the brain tissue away from the perihematomal was taken as the control sample.HE staining and TUNEL method were used to detect apoptotic cells in the tissues around hematoma.The expression of serum Aβand perihematomal tissue Aβwere detected by ELISA and immuno histochemistry respectively.Results The number of apoptosis of perihematomal tissue in the A,B,C,D,E groups were all increased compared with the control sample(P<0.05).The number of apoptosis of perihematomal tissue in the B,C,D,E groups were all increased compared with the A group(P<0.05),which increased first and then decreased with the time of HICH onset to surgery,reaching the highest at 24-48 h.Compared with the A group,the expression of serum Aβin the B,C,D,E groups were all increased(P<0.05),and the number of Aβpositive cells in perihematomal tissue were all increased(P<0.05),which first increased and then decreased with the time of HICH onset to surgery,reaching the highest at 12-<24 h.Compared with the control sample,the number of Aβpositive cells in perihematomal tissue in the A,B,C,D,E groups were all increased(P<0.05).Pearson correlation showed that the level of serum Aβwas positively correlated with the number of apoptosis of perihematomal tissue(r=0.482,P=0.001),and the number of Aβpositive cells in perihematomal tissue was positively correlated with the number of apoptosis of perihematomal tissue(r=0.940,P<0.05).Conclusion A large number of apoptotic cells were found in the tissues around the hematoma in patients with HICH,and high expression of Aβwas found in the serum and tissues around the hematoma in patients with HICH.Serum Aβlevel and the number of Aβpositive cells in the tissues around the hematoma were positively correlated with the number of apoptotic cells in the tissues around the hematoma,suggesting that Aβmay participate in the apoptosis of the tissues around the hematoma in HICH.
Objective To explore the expression of amyloidβ(Aβ)in patients with hypertensive intracerebral hemorrhage(HICH)and its relationship with apoptosis of perihematomal tissue.Methods 42 HICH patients who underwent brain hematoma removal in the hospital from June 2010 to March 2016 were enrolled in the study.According to the time of onset to surgery,42 HICH patients were divided into A group(<6 h,20 cases),B group(6-<12 h,9 cases),C group(12-<24 h,6 cases),D group(24-48 h,4 cases)and E group(>48 h,3 cases).The perihematomal tissue was taken as the research sample and the brain tissue away from the perihematomal was taken as the control sample.HE staining and TUNEL method were used to detect apoptotic cells in the tissues around hematoma.The expression of serum Aβand perihematomal tissue Aβwere detected by ELISA and immuno histochemistry respectively.Results The number of apoptosis of perihematomal tissue in the A,B,C,D,E groups were all increased compared with the control sample(P<0.05).The number of apoptosis of perihematomal tissue in the B,C,D,E groups were all increased compared with the A group(P<0.05),which increased first and then decreased with the time of HICH onset to surgery,reaching the highest at 24-48 h.Compared with the A group,the expression of serum Aβin the B,C,D,E groups were all increased(P<0.05),and the number of Aβpositive cells in perihematomal tissue were all increased(P<0.05),which first increased and then decreased with the time of HICH onset to surgery,reaching the highest at 12-<24 h.Compared with the control sample,the number of Aβpositive cells in perihematomal tissue in the A,B,C,D,E groups were all increased(P<0.05).Pearson correlation showed that the level of serum Aβwas positively correlated with the number of apoptosis of perihematomal tissue(r=0.482,P=0.001),and the number of Aβpositive cells in perihematomal tissue was positively correlated with the number of apoptosis of perihematomal tissue(r=0.940,P<0.05).Conclusion A large number of apoptotic cells were found in the tissues around the hematoma in patients with HICH,and high expression of Aβwas found in the serum and tissues around the hematoma in patients with HICH.Serum Aβlevel and the number of Aβpositive cells in the tissues around the hematoma were positively correlated with the number of apoptotic cells in the tissues around the hematoma,suggesting that Aβmay participate in the apoptosis of the tissues around the hematoma in HICH.
引文
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[12]ZHANG X Q,ZHANG Z M,YIN X L,et al.Exploring the optimal operation time for patients with hypertensive intracerebral hemorrhage:tracking the expression and progress of cell apoptosis of prehematomal brain tissues[J].Chin Med J(Engl),2010,123(10):1246-1250.
[13]聂柳,王洪军,刘兴吉,等.脑出血大鼠颅内压及Bcl-2、Bax表达的变化与血肿周围水肿区细胞凋亡的关系[J].广东医学,2016,37(4):492-495.
[14]鲍刚,王茂德,韩玉梁,等.脑出血血肿周围组织中P75NTR和proNGF的表达及其与细胞凋亡的关系[J].神经解剖学杂志,2010,26(1):78-81.
[2]张钶,霍钢,王晓澍,等.早期强化降压对高血压脑出血患者颅内血肿及水肿的影响[J].第三军医大学学报,2016,38(7):757-760.
[3] GUSHCHA A O,SEMENOV M S,LEPSVERIDZE L T.Experience of endoscopic removal of hypertensive intracerebral hemorrhage[J].Zh Vopr Neirokhir Im N N Burdenko,2015,79(6):71-75.
[4] DING W,CHEN R,WU C,et al.Increased expression of HERPUD1involves in neuronal apoptosis after intracerebral hemorrhage[J].Brain Res Bull,2017,128:40-47.
[5] D′USCIO L V,HE T,KATUSIC Z S.Expression and processing of amyloid precursor protein in vascular endothelium[J].Physiology(Bethesda),2017,32(1):20-32.
[6] LUO J H,WARMLANDER S K,GRASLUND A A.Cross-interactions between the alzheimer disease amyloid-beta peptide and other amyloid proteins:a further aspect of the amyloid cascade hypothesis[J].J Biol Chem,2016,291(32):16485-16493.
[7] HAGLUND M,KALARIA R,SLADE J Y,et al.Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer′s disease and vascular dementia[J].Acta Neuropathol,2006,111(5):430-435.
[8]余猛飞,常成,张俊霞,等.小鼠脊髓损伤后Aβ蛋白的表达与细胞凋亡[J].神经解剖学杂志,2014,30(6):655-660.
[9]中华医学会第四届全国脑血管病学术会议.各项脑血管诊断要点(1995)[J].中华神经内科杂志,1996,29(6):379.
[10]ELMORE S.Apoptosis:a review of programmed cell death[J].Toxicol Pathol,2007,35(4):495-516.
[11]吕建平,骆锦标,曹志恺,等,脑淀粉样血管病脑出血患者血清抗Aβ抗体检测及临床治疗[J].解剖学研究,2013,35(1):32-35.
[12]ZHANG X Q,ZHANG Z M,YIN X L,et al.Exploring the optimal operation time for patients with hypertensive intracerebral hemorrhage:tracking the expression and progress of cell apoptosis of prehematomal brain tissues[J].Chin Med J(Engl),2010,123(10):1246-1250.
[13]聂柳,王洪军,刘兴吉,等.脑出血大鼠颅内压及Bcl-2、Bax表达的变化与血肿周围水肿区细胞凋亡的关系[J].广东医学,2016,37(4):492-495.
[14]鲍刚,王茂德,韩玉梁,等.脑出血血肿周围组织中P75NTR和proNGF的表达及其与细胞凋亡的关系[J].神经解剖学杂志,2010,26(1):78-81.