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[摘要]
目的 探討頭孢曲松對(duì)新生大鼠缺氧缺血性腦損傷(HIBD)的保護(hù)作用,并考察其作用機(jī)制。方法 新生SD大鼠隨機(jī)分為假手術(shù)組、模型組和頭孢曲松組,每組各48只,各組依據(jù)造模成功后觀察時(shí)間點(diǎn)又分為6 h、12 h、24 h、3 d、5 d、7 d 6個(gè)亞組,每個(gè)亞組各8只。假手術(shù)組只做頸部切開(kāi)和右頸總動(dòng)脈分離術(shù),不結(jié)扎。模型組、頭孢曲松組均制備新生大鼠HIBD模型。假手術(shù)組、模型組于術(shù)后ip生理鹽水10 mL/kg,1次/d,連續(xù)3 d;頭孢曲松組于術(shù)后ip注射用頭孢曲松鈉200 mg/kg,1次/d,連續(xù)3 d。熱板法測(cè)試記錄新生大鼠熱板測(cè)試時(shí)間;HE染色后觀察皮質(zhì)腦組織病理變化;Westernblotting法測(cè)定FADD表達(dá)量;免疫組化法檢測(cè)FADD陽(yáng)性表達(dá)細(xì)胞數(shù)。結(jié)果 與模型組比較,頭孢曲松組的熱板測(cè)試時(shí)間在3、5 d時(shí)明顯縮短,差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。通過(guò)光學(xué)顯微鏡觀察發(fā)現(xiàn)頭孢曲松組腦組織細(xì)胞排列尚規(guī)則,體積稍大,呈輕度水腫改變。與模型組比較,頭孢曲松組在各個(gè)時(shí)間點(diǎn)的FADD表達(dá)量和陽(yáng)性表達(dá)細(xì)胞數(shù)明顯降低(P<0.05)。結(jié)論 頭孢曲松可下調(diào)HIBD新生大鼠腦皮質(zhì)FADD表達(dá),減少凋亡發(fā)生,改善行為學(xué)表現(xiàn),發(fā)揮神經(jīng)保護(hù)作用。
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[Abstract]
Objective To study the protective effect of ceftriaxone against hypoxic-ischemic brain injury in neonatal rats, and investigate its mechanism. Methods Neonatal SD rats were randomly divided into Sham group, model group, and ceftriaxone group, and each group was divided into 6 h, 12 h, 24 h, 3 d, 5 d, and 7 d subgroup with 8 rats according to observation time. Rats in the Sham group were performed only by incision of neck and right common carotid artery dissection without ligation. Rats in the ceftriaxone group and model group were successfully established hypoxic ischemic brain damage (HIBD) models. Rats in the Sham group and model group were ip administered with normal saline after the operation, 10 mL/kg, once daily, treated for 3 d. Rats in the ceftriaxone group were ip administered with Ceftriaxone Sodium for injection after the operation, 200 mg/kg, once daily, treated for 3 d. Hot plate test method was used to record hot plate test time in neonatal rats. HE staining was used to observe the pathological changes of cortex. FADD expression was detected by Western blotting method. The number of FADD positive cells was detected by immunohistochemical staining. Results Compared with the model group, hot plate test time in the ceftriaxone group were significantly shorter on days 3 and 5, and there were differences between two groups (P<0.05). By optical microscope observation, brain tissue cell arrangement in ceftriaxone group was still rule, the volume slightly larger, and a slight edema changes. Compared with the model group, FADD expression and positive cells numbers in the ceftriaxone group were obviously decreased at various time points, (P<0.05). Conclusion Ceftriaxone can down-regulate FADD expression in cerebral cortex of neonatal rats with HIBD, reduce neuron cell apoptosis, improve behaviors, and play neuroprotective effect.
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