痰浊眩晕家兔模型的建立及巨噬细胞功能和粘附分子表达研究
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摘要
目的:通过高脂饲料喂养结合颈部局部注射组织硬化剂建立痰浊眩晕家兔模型,探讨巨噬细胞功能及粘附分子表达变化在痰邪致病中的作用。
方法:随机将40只家兔分为对照组、模型组、化痰组、化瘀组、西药组,除对照组外均采用高脂饲料喂养结合颈部局部注射组织硬化剂建立痰浊眩晕家兔模型,化痰组、化瘀组和西药组分别给予半夏白术天麻汤、通窍活血汤和盐酸氟桂利嗪治疗,对照组和模型组灌胃生理盐水作对照,比色法测定血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C),BL-410生物机能实验系统记录转颈诱发眼震电图,称量体重并舌苔照相,进行椎-基底动脉血流多普勒彩色超声检测,椎动脉组织病理学HE染色检测及超微病理学检测,流式细胞术检测血液单核细胞吞噬功能,实时荧光定量PCR检测椎动脉组织单核细胞趋化蛋白-1(MCP-1),免疫组织化学检测椎动脉粘附分子CD54表达并进行图像分析。
结果:与对照组比较,模型组TC、TG和LDL-C显著增高(P<0.01),眼震出现率和眼震持续时间明显增加(P<0.01),体重增加明显(P<0.01),舌苔厚腻(对照组为薄白),椎-基底动脉血流多普勒彩色超声显示双侧椎动脉及基底动脉的收缩期血流速度、舒张期血流速度和平均血流速度均降低(P<0.01),椎动脉病理组织HE染色可见内膜下泡沫细胞形成及脂质沉积、管壁明显增厚、管腔明显变小、管腔直径与中膜厚度比明显降低、中膜平滑肌细胞排列紊乱(对照组椎动脉管壁较薄、管腔较大、内膜结构完整、中膜平滑肌细胞排列整齐),超微病理学检测显示内弹力膜不完整、内皮下单核细胞粘附及向内膜下迂移、平滑肌细胞穿透内弹力膜向外迁移、胶原纤维明显增多及排列紊乱、可见平滑肌细胞核固缩、染色质边集、有脂质样颗粒沉积于细胞间隙(对照组内弹力膜完整、平滑肌纤维正常、排列紧密、胶原纤维排列规则、无增生),单核细胞吞噬率上升(P<0.05),MCP-1 mRNA表达水平明显升高(P<0.01),粘附分子CD54阳性表达比例明显增加(P<0.01)。与模型组比较,化痰组TC、TG和LDL-C明显降低(P<0.01),眼震出现率减少(P<0.05),眼震持续时间缩短(P<0.0 1),体重降低(P<0.05),舌苔已接近薄白,椎-基底动脉血流多普勒彩色超声显示双侧椎动脉及基底动脉的收缩期血流速度显著增加(P<0.01),舒张期血流速度和平均血流速度均也增加(P<0.05),病理学和超微病理学检测结果有明显改善,单核细胞吞噬率下降(P<0.05),MCP-1 mRNA表达水平降低(P<0.05),粘附分子cD54阳性表达比例减少(P<0.01);化瘀组和西药组TC、TG和LDL-C降低不明显(P>0.05),眼震出现率减少不明显(P>0.05),眼震持续时间缩短(P<0.05),体重无明显降低(P>0.05),舌苔仍为腻苔,椎-基底动脉血流多普勒彩色超声显示双侧椎动脉及基底动脉的收缩期血流速度明显增加(P<0.01),舒张期血流速度和平均血流速度均有增加(P<0.05),病理学和超微病理学检测结果改善不佳,单核细胞吞噬率下降不明显(P>0.05),MCP-1 mRNA表达水平无降低(P>0.05),粘附分子CD54阳性表达比例不减少(P>0.05)。
结论:所制作模型为痰浊眩晕病证结合家兔模型,存在单核巨噬细胞趋化和活化,粘附分子表达增强,进一步提示单核巨噬系统细胞的趋化和活化及粘附分子表达增强在痰邪致病中发挥极重要的作用。
Objective
To establish the model of rabbit's vertigo due to phlegm-turbidity, this paper applied combination of high-fat diet and injecting the neck with sclerosant.Macrophage function and expression of adhesion molecule were evaluated in phlegm evil pathopoiesis.
Methods
40 rabbits were randomly divided into control group,model group,dissipate phlegm group,dissipate blood stasis group, western medicine group.The rabbits were fed high fat diet combined with injecting neck with sclerosant to establish phlegm-turbidity rabbit model of vertigo without the control group.Dissipate phlegm group were given Banxia-Baizhu-Tianma decoction,dissipate blood stasis group were given Tongqiao-Huoxue decoction and western medicine group were given flunarizine hydrochloride,while the control group and model group were administered with normal saline. Colorimetry was determined serum total cholesterol(TC), triglyceride(TG) and low density lipoprotein cholesterol(LDL-C). BL-410 biological function recorded experimental system was detected induced cervical electronystagmogram(ENG).Body weight of rabbits was measured and photograph of coated tongue was taked. Transcranial doppler sonography was used to measure vertebral-basilar artery blood flow.The vertebral artery was detected with histopathological hematoxylin-eosin staining and ultrastructural pathology by transmission electron microscope.Flow cytometry was determined phagocytic function of blood monocyte.Vertebral artery organizations monocyte chemoattractant protein-1(MCP-1) was detected by real-time fluorescence quantitative PCR.Image analysis was applied for vertebral artery expression of adhesion molecules CD54 immunohistochemistry.
Results
Compared wi th the control group,TC,TG and LDL-C of model group was significantly higher(P<0.01),rate of nystagmus and nystagmus duration increased significantly(P<0.01),weight gained significantly (P<0.01),tongue coated thick-greasy(the control group coated thin-white),transcranial doppler sonography of vertebral-basilar artery showed bi lateral vertebral artery and basilar artery systolic blood flow velocity,diastolic blood flow velocity and mean flow velocity decreased(P<0.01),vertebral artery pathology of HE staining shows that the formation of foam cells and lipid deposition,marked wall thickening,lumen significantly smaller, ratio of lumen diameter to media thickness was lower,smooth muscle cells disordered(vertebral artery wall of the control group was thinner,larger lumen,intima structural integrity,and has neatly arranged smooth muscle cells),ultrastructural pathology showed incomplete internal elastic membrane,endothelial adhesion of monocytes to the subendocardial migration,smooth muscle cells penetrating the internal elastic membrane outward migration, increased collagen fibers with disorder,nucleus of smooth muscle cell shrinkage,chroma tin margination,a lipid-like particles deposited on cell gap(the control group showed the internal elastic membrane integrity,smooth muscle fibers being normal and closely, collagen fibers arranged regularly and non-proliferatively),the rate of monocyte phagocytosis increased(P<0.05),MCP-1 mRNA expression was significantly increased(P<0.01),the ratio of adhesion molecule CD54 positive expression increased significantly (P<0.01).Compared with the model group,TC,TG and LDL-C of dissipate phlegm group decreased significantly(P<0.01),the occurrence of nystagmus reduced(P<0.05),shortened the duration of nystagmus(P<0.01),weight loss(P<0.05),coated tongue closed to thin white,transcranial doppler sonography of vertebral-basilar artery showed bilateral vertebral artery and basilar artery systolic blood flow velocity increased significantly(P<0.01), diastolic blood flow velocity and mean flow velocity increased (P<0.05),pathology and ultrastructural pathology results improved, rate of monocyte phagocytosis decreased(P<0.05),expression of MCP-1 mRNA lower(P<0.05),positive expression of adhesion molecules CD54 reduced(P<0.01).TC,TG and LDL-C lowering of dissipate blood stasis group and western medicine group was not obvious(P>0.05),reduced the occurrence of nystagmus was not obvious(P>0.05),the duration of nystagmus shorten(P<0.05), weight loss was not obvious(P>0.05),still greasy tongue coating, transcranial doppler sonography of vertebral-basilar artery showed bilateral vertebral artery and basilar artery systolic blood markedly increased in flow velocity(P<0.01),diastolic blood flow velocity and mean velocity increased(P<0.05),pathology and ultrastructural pathology results did not improve obviously,rate of mononuclear phagocytic did not decrease significant(P>0.05), expression of MCP-1 mRNA did not decrease obviously(P>0.05), positive expression of adhesion molecules CD54 did not reduce the proportion obviously(P>0.05).
Conclusions
The produced model was rabbit's vertigo due to phlegm-turbidity. The model existed mononuclear macrophages activated and chemotaxis, adhesion molecule expression increased.It further showed that monocyte macrophage system cells activation and chemotaxis with increased expression of adhesion molecule play a very important role in the phlegm pathogen.
方法:随机将40只家兔分为对照组、模型组、化痰组、化瘀组、西药组,除对照组外均采用高脂饲料喂养结合颈部局部注射组织硬化剂建立痰浊眩晕家兔模型,化痰组、化瘀组和西药组分别给予半夏白术天麻汤、通窍活血汤和盐酸氟桂利嗪治疗,对照组和模型组灌胃生理盐水作对照,比色法测定血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C),BL-410生物机能实验系统记录转颈诱发眼震电图,称量体重并舌苔照相,进行椎-基底动脉血流多普勒彩色超声检测,椎动脉组织病理学HE染色检测及超微病理学检测,流式细胞术检测血液单核细胞吞噬功能,实时荧光定量PCR检测椎动脉组织单核细胞趋化蛋白-1(MCP-1),免疫组织化学检测椎动脉粘附分子CD54表达并进行图像分析。
结果:与对照组比较,模型组TC、TG和LDL-C显著增高(P<0.01),眼震出现率和眼震持续时间明显增加(P<0.01),体重增加明显(P<0.01),舌苔厚腻(对照组为薄白),椎-基底动脉血流多普勒彩色超声显示双侧椎动脉及基底动脉的收缩期血流速度、舒张期血流速度和平均血流速度均降低(P<0.01),椎动脉病理组织HE染色可见内膜下泡沫细胞形成及脂质沉积、管壁明显增厚、管腔明显变小、管腔直径与中膜厚度比明显降低、中膜平滑肌细胞排列紊乱(对照组椎动脉管壁较薄、管腔较大、内膜结构完整、中膜平滑肌细胞排列整齐),超微病理学检测显示内弹力膜不完整、内皮下单核细胞粘附及向内膜下迂移、平滑肌细胞穿透内弹力膜向外迁移、胶原纤维明显增多及排列紊乱、可见平滑肌细胞核固缩、染色质边集、有脂质样颗粒沉积于细胞间隙(对照组内弹力膜完整、平滑肌纤维正常、排列紧密、胶原纤维排列规则、无增生),单核细胞吞噬率上升(P<0.05),MCP-1 mRNA表达水平明显升高(P<0.01),粘附分子CD54阳性表达比例明显增加(P<0.01)。与模型组比较,化痰组TC、TG和LDL-C明显降低(P<0.01),眼震出现率减少(P<0.05),眼震持续时间缩短(P<0.0 1),体重降低(P<0.05),舌苔已接近薄白,椎-基底动脉血流多普勒彩色超声显示双侧椎动脉及基底动脉的收缩期血流速度显著增加(P<0.01),舒张期血流速度和平均血流速度均也增加(P<0.05),病理学和超微病理学检测结果有明显改善,单核细胞吞噬率下降(P<0.05),MCP-1 mRNA表达水平降低(P<0.05),粘附分子cD54阳性表达比例减少(P<0.01);化瘀组和西药组TC、TG和LDL-C降低不明显(P>0.05),眼震出现率减少不明显(P>0.05),眼震持续时间缩短(P<0.05),体重无明显降低(P>0.05),舌苔仍为腻苔,椎-基底动脉血流多普勒彩色超声显示双侧椎动脉及基底动脉的收缩期血流速度明显增加(P<0.01),舒张期血流速度和平均血流速度均有增加(P<0.05),病理学和超微病理学检测结果改善不佳,单核细胞吞噬率下降不明显(P>0.05),MCP-1 mRNA表达水平无降低(P>0.05),粘附分子CD54阳性表达比例不减少(P>0.05)。
结论:所制作模型为痰浊眩晕病证结合家兔模型,存在单核巨噬细胞趋化和活化,粘附分子表达增强,进一步提示单核巨噬系统细胞的趋化和活化及粘附分子表达增强在痰邪致病中发挥极重要的作用。
Objective
To establish the model of rabbit's vertigo due to phlegm-turbidity, this paper applied combination of high-fat diet and injecting the neck with sclerosant.Macrophage function and expression of adhesion molecule were evaluated in phlegm evil pathopoiesis.
Methods
40 rabbits were randomly divided into control group,model group,dissipate phlegm group,dissipate blood stasis group, western medicine group.The rabbits were fed high fat diet combined with injecting neck with sclerosant to establish phlegm-turbidity rabbit model of vertigo without the control group.Dissipate phlegm group were given Banxia-Baizhu-Tianma decoction,dissipate blood stasis group were given Tongqiao-Huoxue decoction and western medicine group were given flunarizine hydrochloride,while the control group and model group were administered with normal saline. Colorimetry was determined serum total cholesterol(TC), triglyceride(TG) and low density lipoprotein cholesterol(LDL-C). BL-410 biological function recorded experimental system was detected induced cervical electronystagmogram(ENG).Body weight of rabbits was measured and photograph of coated tongue was taked. Transcranial doppler sonography was used to measure vertebral-basilar artery blood flow.The vertebral artery was detected with histopathological hematoxylin-eosin staining and ultrastructural pathology by transmission electron microscope.Flow cytometry was determined phagocytic function of blood monocyte.Vertebral artery organizations monocyte chemoattractant protein-1(MCP-1) was detected by real-time fluorescence quantitative PCR.Image analysis was applied for vertebral artery expression of adhesion molecules CD54 immunohistochemistry.
Results
Compared wi th the control group,TC,TG and LDL-C of model group was significantly higher(P<0.01),rate of nystagmus and nystagmus duration increased significantly(P<0.01),weight gained significantly (P<0.01),tongue coated thick-greasy(the control group coated thin-white),transcranial doppler sonography of vertebral-basilar artery showed bi lateral vertebral artery and basilar artery systolic blood flow velocity,diastolic blood flow velocity and mean flow velocity decreased(P<0.01),vertebral artery pathology of HE staining shows that the formation of foam cells and lipid deposition,marked wall thickening,lumen significantly smaller, ratio of lumen diameter to media thickness was lower,smooth muscle cells disordered(vertebral artery wall of the control group was thinner,larger lumen,intima structural integrity,and has neatly arranged smooth muscle cells),ultrastructural pathology showed incomplete internal elastic membrane,endothelial adhesion of monocytes to the subendocardial migration,smooth muscle cells penetrating the internal elastic membrane outward migration, increased collagen fibers with disorder,nucleus of smooth muscle cell shrinkage,chroma tin margination,a lipid-like particles deposited on cell gap(the control group showed the internal elastic membrane integrity,smooth muscle fibers being normal and closely, collagen fibers arranged regularly and non-proliferatively),the rate of monocyte phagocytosis increased(P<0.05),MCP-1 mRNA expression was significantly increased(P<0.01),the ratio of adhesion molecule CD54 positive expression increased significantly (P<0.01).Compared with the model group,TC,TG and LDL-C of dissipate phlegm group decreased significantly(P<0.01),the occurrence of nystagmus reduced(P<0.05),shortened the duration of nystagmus(P<0.01),weight loss(P<0.05),coated tongue closed to thin white,transcranial doppler sonography of vertebral-basilar artery showed bilateral vertebral artery and basilar artery systolic blood flow velocity increased significantly(P<0.01), diastolic blood flow velocity and mean flow velocity increased (P<0.05),pathology and ultrastructural pathology results improved, rate of monocyte phagocytosis decreased(P<0.05),expression of MCP-1 mRNA lower(P<0.05),positive expression of adhesion molecules CD54 reduced(P<0.01).TC,TG and LDL-C lowering of dissipate blood stasis group and western medicine group was not obvious(P>0.05),reduced the occurrence of nystagmus was not obvious(P>0.05),the duration of nystagmus shorten(P<0.05), weight loss was not obvious(P>0.05),still greasy tongue coating, transcranial doppler sonography of vertebral-basilar artery showed bilateral vertebral artery and basilar artery systolic blood markedly increased in flow velocity(P<0.01),diastolic blood flow velocity and mean velocity increased(P<0.05),pathology and ultrastructural pathology results did not improve obviously,rate of mononuclear phagocytic did not decrease significant(P>0.05), expression of MCP-1 mRNA did not decrease obviously(P>0.05), positive expression of adhesion molecules CD54 did not reduce the proportion obviously(P>0.05).
Conclusions
The produced model was rabbit's vertigo due to phlegm-turbidity. The model existed mononuclear macrophages activated and chemotaxis, adhesion molecule expression increased.It further showed that monocyte macrophage system cells activation and chemotaxis with increased expression of adhesion molecule play a very important role in the phlegm pathogen.
引文
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