创伤性脑损伤后亚低温治疗对细胞间粘附分子-1表达的影响

目的 :探讨早期应用亚低温治疗对创伤性脑损伤后细胞间粘附分子 1(ICAM 1)表达的影响。方法 :采用Feeney自由落体改良模型 ,设定假颅脑外伤模型组、颅脑外伤模型组及亚低温组。取伤灶区脑组织检测髓过氧化物酶 (MPO)活性 ,作ICAM 1免疫组织化学染色 ,光境下计数ICAM 1阳性血管数 ,同时通过半定量逆转录 聚合酶链式反应 (RT PCR)检测ICAM 1基因mRNA的表达。结果 :亚低温组伤灶侧脑组织中ICAM 1阳性血管数及ICAM 1mRNA表达量均显著低于颅脑外伤模型组 (P <0 .0 1)。亚低温组MPO活性明显低于颅脑外伤模型组 (P <0 .0 1)。结论 :早期应用亚低温治疗能明显减少伤灶区脑组织中ICAM 1的表达及中性粒细胞浸润 ,有助于改善创伤性脑损伤后炎症反应所引起的继发性脑损伤     

神经再生复合剂对大鼠急性脊髓损伤后其内MDA、SOD和MPO表达的影响

目的:观察促神经再生因子复合剂N6对大鼠急性脊髓损伤后脊髓及血清丙二醛(MDA)、超氧化物歧化酶(SOD)及脊髓内髓过氧化物酶(MPO)表达的影响,探讨其减轻继发性损伤的作用机制及保护受损脊髓作用的最佳介入时间。方法:用改良Allen’s打击法制备大鼠急性脊髓损伤模型,假手术组打开椎板不损伤脊髓,模型组造模后不予治疗,对照组分别于脊髓损伤后10、30和60 min向腹腔注射甲级强的松龙(30 mg/kg),实验组分别于脊髓损伤后10、30和60 min向蛛网膜下腔注射促神经再生因子复合剂N6(166μg/kg)。造模后24 h取材,于各时间点测得假手术组、模型组、实验组和对照组大鼠脊髓损伤组织及血清中MDA、SOD及损伤脊髓组织的MPO活性。结果:实验组损伤脊髓组织MDA含量随着药物介入时间的延迟而增高,各时间点间MDA含量无显著性差异(P>0.05);血清MDA含量随着药物介入时间的延迟而增高,60 min与10、30 min相比有显著性差异(P<0.05);实验组损伤脊髓组织SOD含量随着药物介入时间的延迟而降低,各时间点间SOD含量无显著性差异(P>0.05);血清SOD含量随着药物介入时间的延迟而降低,60 min与10 min相比有显著性差异(P<0.05);实验组损伤脊髓组织MPO含量随着药物介入时间的延迟而增高,60 min与10 min相比有显著性差异(P<0.05)。结论:促神经再生因子复合剂N6治疗可以提高急性脊髓损伤大鼠损伤脊髓及血清SOD含量,降低损伤脊髓及血清MDA、损伤脊髓MPO的含量,从而降低急性脊髓损伤后的继发性损伤,达到保护脊髓组织的目的,且介入治疗时间越早,疗效越好。     

Rapamycin protects against middle cerebral artery occlusion induced focal cerebral ischemia in rats

Stroke is a major cause of mortality and disability. The management with thrombolytic therapy has to be initiated within 3-4 h and is associated with limitations like increased risk of intracranial hemorrhage and progression of cerebral injury. Immunophilin inhibitors such as cyclosporine A and tacrolimus have been shown to afford neuroprotection by improving neurological functions and infarct volume in models of ischemic stroke. In the present study, the effect of rapamycin in middle cerebral artery occlusion (MCAo) model of ischemic stroke was evaluated.Ischemic stroke was induced in rats by occluding the MCA using the intraluminal thread. After 1 h of MCAo, animals were administered rapamycin (50, 150, 250 μg/kg, i.p.). After 2 h of occlusion, reperfusion was done. Thirty minutes after reperfusion, animals were subjected to diffusion-weighted magnetic resonance imaging for assessment of protective effect of rapamycin. Twenty-four hours after MCAo, motor performance was assessed, the animals were euthanized and the brains were removed for estimation of malondialdehyde, glutathione, nitric oxide and myeloperoxidase.Significant improvement was observed with rapamycin 150 and 250 μg/kg in percent infarct area, apparent diffusion coefficient and signal intensity as compared to vehicle treated group. Rapamycin treatment ameliorated motor impairment associated with MCAo and significantly reversed the changes in levels of malondialdehyde, glutathione, nitric oxide and myeloperoxidase.The results of the present study indicate neuroprotective effect of rapamycin in MCAo model of stroke. Therefore, rapamycin might be considered as a therapeutic strategy for stroke management.     

Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties

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Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.     

姜黄素对肝缺血再灌注损伤保护作用的研究

目的探讨姜黄素对自体肝移植大鼠肝脏缺血再灌注损伤(IRI)的保护作用及其可能机制。方法54只SD雄性大鼠随机分为假手术(SO)组、自体肝移植模型姜黄素预处理(CU)组以及自体肝移植模型溶剂对照(CM)组,术后或再灌注2,6,24 h每组分别处死6只大鼠进行谷丙转氨酶(ALT)、谷草转氨酶(AST)、髓过氧化物酶(Myeloperoxidase MPO)的含量检测。结果血清ALT及AST水平,CM组及CU组均较SO组明显升高,但CM组又明显高于CU组;MPO在SO组含量明显低于CM组和CU组,而CU组又显著低于CM组。结论姜黄素对自体肝移植大鼠肝缺血再灌注损伤有保护作用,其机制可能与减轻中性粒细胞浸润有关。     

Antiulcerogenic activity of hydroalcoholic fruit extract of Pithecellobium dulce in different experimental ulcer models in rats

Ethnopharmacological relevance

The ethnopharmacological importance of Pithecellobium dulce is evidenced by its traditional use for gastric complications. The aim of the study is to evaluate the gastroprotective activity and the mechanism of action of hydroalcoholic fruit extract of P. dulce (HAEPD) in rats by using chemical and stress induced ulcer models.

Materials and methods

Gastric ulcer was induced by administering alcohol (or) acetylsalicylic acid (or) hypothermic restraint stress to rats pretreated with HAEPD (200 mg/kg b wt for 30 day). Volume of gastric fluid, pH, acidity, activities of pepsin, H⁺, K⁺-ATPase, myeloperoxidase, mucin content, nucleic acids, glycoproteins and prostaglandin E₂ (PGE₂) levels were assessed in gastric tissues.

Results

Ulcer score was significantly minimized in HAEPD administered animals. pH and acidity of gastric fluid were significantly minimized and the mucin, PGE₂ levels were significantly maintained in drug pre administered animals. The activities of H⁺, K⁺- ATPase and myeloperoxidase were found to be significantly elevated in ulcer control animals and found to be decreased in drug pretreated animals. The cell proliferation was found to be enhanced in drug received animals. The total protein bound carbohydrate to total protein ratio was found to be significantly maintained by HAEPD. The effects were found to be comparable with that of standard drug omeprazole.

Conclusion

It is concluded that HAEPD possess a potent antiulcer activity probably by acting as cytoprotective and antiacid secretory agent.