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目的:研究羟基喜树碱(HCPT)缓释片对大鼠的脑组织毒性及骨髓抑制作用。方法:将大鼠随机分为正常对照组、假手术组和低、中、高剂量(HCPT∶聚乳酸(PLA)分别为1∶10、1∶5、1∶1)HCPT组,每组12只,HCPT组脑内植入相应规格的HCPT缓释片1片,假手术组行假手术模拟机械损伤。术后30d分别采用苏木精-伊红(HE)染色观察各组大鼠脑组织病理变化;尼氏染色观察神经元活性;原位末端标记试剂盒(TUNEL)染色观察神经元凋亡情况;瑞氏染色观察骨髓抑制情况。结果:与正常对照组比较,其余各组大鼠脑组织均有不同程度的损伤,受损部位均出现胶质细胞增生,神经元凋亡明显(P<0.01),但均未见发生骨髓抑制。与假手术组比较,中、高剂量HCPT组脑组织受损部位出现纤维化及坏死现象,神经元活性降低,神经元凋亡明显(P均<0.01),低剂量HCPT组上述指标均无明显变化。结论:脑内植入HCPT缓释片对大鼠脑组织具有一定程度的毒性,但未引起骨髓抑制。
Objective: To study the toxicity and bone marrow suppression of HCPT sustained release tablets in rats. Methods: The rats were randomly divided into normal control group, sham operation group and low, medium and high dose HCPT group (HCPT: PLA: 1:10, 1: 5, Only one HCPT group was implanted with one HCPT sustained-release tablets intracerebrally and the sham-operated group was sham-operated to simulate mechanical injury. Thirty days after operation, hematoxylin and eosin (HE) staining was used to observe the pathological changes of brain tissue in each group. Nissl staining was used to observe the neuronal activity. TUNEL staining was used to observe neuronal apoptosis. Wright’s stain observed bone marrow suppression. Results: Compared with the normal control group, the rats in the other groups all had different degrees of damage in the brain tissue. Glial cell proliferation and neuronal apoptosis were found in the damaged sites (all P <0.01), but no bone marrow suppression occurred . Compared with the sham operation group, the HCPT group showed fibrosis and necrosis, neuron activity decreased and neuron apoptosis significantly (P <0.01), but no significant difference between the low and medium dose HCPT groups Variety. Conclusion: The intracerebral implantation of HCPT sustained release tablets has a certain degree of toxicity on rat brain, but does not cause bone marrow suppression.