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目的:探讨急、慢性甲基苯丙胺(METH)毒性所导致的大鼠心肌形态学和心功能指标的变化。方法:Wistar大鼠分别造成METH急性及慢性中毒动物模型,各自设立对照组。对照组注射等量生理盐水,其余处理同实验组。用药后观察大鼠的行为变化并进行评分;监测其心率及血压变化。造模结束后用10%的水合氯醛腹腔注射麻醉,腹主动脉促凝管采集血液标本并分离血清,采用双抗夹心酶联免疫吸附法(ELISA)测定血清BNP和Tn-T。迅速打开胸腔摘取心脏,大体观察称重、HE染色观察有无组织病理学改变。结果:(1)急性METH中毒大鼠行为活动明显增多,主要为:直立探索、攀爬、鼻嗅等动作,行为学评分与对照组相比差异有显著性(F=349.057,P<0.001);心率和平均动脉压显著高于对照组(F=1051.599,P<0.001;F=373.974,P<0.001);心肌大体观察未见明显异常;HE染色切片可见局灶性心肌纤维断裂,肌溶灶形成并可见部分区域心肌收缩带坏死;血清中Tn-T含量明显升高,差异有显著性意义(t=9.566,P<0.001),血清BNP的含量无显著性变化(t=1.407,P=0.177)。(2)慢性METH中毒大鼠注射METH后有明显的直立探索、攀爬、鼻嗅等行为增多,行为学评分与对照组相比差异有显著性(F=602.887,P<0.001);心率和平均动脉压显著高于对照组(F=2723.644,P<0.001;F=413.556,P<0.001);大鼠心肌大体观察未见明显异常;HE染色切片可见心肌细胞排列紊乱,可见粗颗粒样变、嗜酸性变、细胞空泡性变、局灶性肌纤维溶解、断裂以及纤维性变;慢性METH组大鼠血清中Tn-T和BNP含量均显著升高,差异有统计学意义(t=10.188,P<0.001;t=10.716,P<0.001)。结论:METH短期大剂量和长期应用均可对大鼠心肌造成明显的毒性损伤,如可引起刻板行为增多,心率和血压升高,心脏切片可观察到明显的心肌细胞损伤,造成心肌损伤标志物Tn-T的升高。急性METH中毒因用药时间较短,并未引起心脏功能的损害,而慢性METH中毒则可引起BNP含量的明显升高,说明已经对心脏功能造成影响。
Objective: To investigate the morphological and cardiac function changes of myocardium caused by acute and chronic METH toxicity. Methods: Wistar rats were caused acute and chronic METH poisoning animal models, the establishment of a control group. The control group was injected with the same amount of saline, the rest treated with the experimental group. The rats were observed behavioral changes and scored after treatment; monitoring of heart rate and blood pressure changes. After modeling, 10% chloral hydrate was intraperitoneally injected into the abdominal cavity to collect blood samples and serum was separated. Serum BNP and Tn-T were measured by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Quickly open the chest to remove the heart, the general observation of weight, HE staining to observe whether the histopathological changes. Results: (1) Behavior of acute METH poisoned rats increased significantly, mainly including upright exploration, climbing and nasal snorting. The scores of behavioral score were significantly different from those of the control group (F = 349.057, P <0.001) ; Heart rate and mean arterial pressure were significantly higher than those in the control group (F = 1051.599, P <0.001; F = 373.974, P <0.001); no obvious abnormalities were observed in grossly observed myocardium; focal myocardial fibrillation Tumor necrosis and myocardial necrosis were found in some of the lesions. The content of Tn-T in serum was significantly increased (t = 9.566, P <0.001), while the content of serum BNP did not change significantly (t = 1.407, P = 0.177). (2) There was a significant upright exploration, climbing and sniffing behavior in METH after chronic METH poisoning. The behavioral score was significantly different from that of the control group (F = 602.887, P <0.001) Mean arterial pressure was significantly higher than that of the control group (F = 2723.644, P <0.001; F = 413.556, P <0.001); no obvious abnormality was found in the grossly observed myocardium of rats; HE staining showed irregular arrangement of cardiomyocytes, , Eosinophilic changes, cell vacuolar changes, focal muscle fiber lysis, rupture and fibrosis; Tn-T and BNP levels in serum of chronic METH group were significantly increased, the difference was statistically significant (t = 10.188 , P <0.001; t = 10.716, P <0.001). CONCLUSION: Both METH and short-term administration can cause obvious toxic injury to the myocardium of rats, such as increased stereotyped behaviors, elevated heart rate and blood pressure, obvious cardiomyocyte damage in cardiac sections and myocardial damage markers Tn-T rise. Acute METH poisoning due to medication time is short, did not cause damage to cardiac function, and chronic METH poisoning can cause a significant increase in BNP levels, indicating that cardiac function has been affected.