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目的探讨细菌脂多糖(LPS)对不同成熟度新生小鼠脑发育的影响。方法 2日龄新生小鼠80只随机分成4组,分别腹腔注射不同剂量(0.3 mg.kg-1、0.6 mg.kg-1、0.9 mg.kg-1)的LPS和等容积的9 g.L-1盐水,观察给药后小鼠的一般情况;测定给药后脑组织IL-6水平、体质量变化以及相对肝质量;2日龄和7日龄的新生小鼠各20只,不同日龄的新生小鼠随机分成感染组(腹腔注射0.6 mg.kg-1LPS)和对照组(腹腔注射等容积的9 g.L-1盐水),连续给药5 d,均至12日龄时,灌注取脑,应用免疫组织化学技术检测各组小鼠脑组织碱性髓鞘蛋白(MBP)、神经元特异性烯醇化酶(NSE)、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)的表达情况。结果 0.6 mg.kg-1LPS腹腔注射可导致新生小鼠体质量增长缓慢、肝大、脑组织IL-6水平升高(Pa<0.05),随着LPS剂量增加,病死率增高,IL-6水平未再升高。2日龄感染组小鼠MBP、NSE表达均明显减少,而Caspase-3的表达明显增多(Pa<0.05);7日龄感染组的MBP表达无明显减少(P>0.05),而NSE的表达明显减少,Caspase-3的表达明显增多(Pa<0.05)。结论新生小鼠腹腔注射0.6 mg.kg-1LPS可以模拟临床感染;2日龄新生小鼠感染不仅影响脑白质髓鞘发育,同时也影响灰质神经元;而脑发育相对成熟的7日龄新生小鼠感染主要影响皮质神经元的发育。
Objective To investigate the effects of bacterial lipopolysaccharide (LPS) on the brain development of neonatal mice with different maturity. Methods Two-day-old neonatal mice were randomly divided into 4 groups. The mice were injected intraperitoneally with different doses of LPS (0.3 mg.kg-1, 0.6 mg.kg-1, 0.9 mg.kg-1) and 9 gL- 1 saline to observe the general situation of the mice after administration; determine the level of IL-6 in the brain tissue, the change of body weight and the relative liver mass after administration; 20 newborn mice of 2 days and 7 days of age, Newborn mice were randomly divided into infection group (intraperitoneal injection of 0.6 mg.kg-1LPS) and control group (intraperitoneal injection of equal volume of 9 gL-1 saline), continuous administration of 5 d, were 12 days old, perfusion brain, Immunohistochemistry was used to detect the expression of MBP, NSE and Caspase-3 in the brain tissue of each group . Results The intraperitoneal injection of 0.6 mg.kg-1 LPS resulted in a slow increase of body weight and increased level of IL-6 in liver and brain (P <0.05). With the increase of LPS dose, the mortality increased and the level of IL-6 No further increase. The expression of MBP and NSE in 2-day-old infected mice was significantly decreased, while the expression of Caspase-3 was significantly increased (P <0.05). The expression of MBP was not significantly decreased in 7-day-old infected mice Obviously, the expression of Caspase-3 increased significantly (Pa <0.05). Conclusion Newborn mice intraperitoneally injected with 0.6 mg.kg-1 LPS can simulate clinical infection; 2-day-old neonatal mouse infection not only affects the white matter myelin development, but also affect the gray matter neurons; and brain development is relatively mature 7-day-old neonate Infection mainly affects the development of cortical neurons.