Study on cerebral edema in the rat model with closed craniocerebral injury and its relationship with apoptosis, inflammatory factor generation and AQPs expression

Objective:To study the relationship of cerebral edema with apoptosis, inflammatory factor generation and AQPs expression in the rat model with closed craniocerebral injury.Methods:Male SD rats were selected as experimental animals and divided into model group and control group. Model group were established into the closed craniocerebral injury models and control group received sham operation. The water content of damaged brain tissue as well as the expression of apoptosis molecules, the generation of inflammatory factors and the expression of aquaporins (AQPs) molecules were measured 7 d after model establishment.Results:The water content of brain tissue of model group was significantly higher than that of control group;Homer1a, Pim-3, Bcl-2, AQP1, AQP4 and AQP9 mRNA expression in brain tissue of model group were significantly lower than those of control group while Cdk5, FasL and Caspase-3 mRNA expression as well as NF-kB, TNF-α, IL-1β, IL-6 and p-JNK generation were significantly higher than those of control group. Homer1a, Pim-3, Bcl-2, AQP1, AQP4 and AQP9 mRNA expression in brain tissue of model group were negatively correlated with water content while Cdk5, FasL and Caspase-3 mRNA expression as well as NF-kB, TNF-α, IL-1β, IL-6 and p-JNK generation were positively correlated with water content.Conclusion:The excessive apoptosis, increased inflammatory factor generation and decreased AQPs expression are closely related to the occurrence of cerebral edema in the process of closed craniocerebral injury.

Isosteroidal Alkaloids from Fritillaria verticillata Willd. and Their NMR Spectroscopic Characteristics

Chemical investigation of Fritillaria verticillata Willd.led to the isolation of eight novel isosteroidal alkaloids(1—4,6,9—11)and four known alkaloids(5,7—8,12),including three unprecedented cis-fused D/E(13α,17α)cevanine alkaloids(1—3),one rarely cis-fused E/F(22α)cevanine alkaloid(6),and one uncommon 5β-jervine-type isosteroidal alkaloid featuring a cis-fused A/B ring moiety(11).In order to establish the structures of 1,the calculated NMR with DP4+evaluation was applied from the plausible structure candidates.The characteristic proton signals for distinguishing D/E conjunction of cevanine alkaloids were summarized.In addition,some proton and carbon signalsαto nitrogen in 6 and 7 are unobservable due to the 14N nuclear quadrupolar relaxation,based on the NMR experiments in different solvents,calculated NMR method and X-ray technology,their structures were determined.The NMR characteristics of cevanine alkaloids to distinguish orientation of long-pair on nitrogen atom withβ-hydroxyl at C-20 were also concluded.The anti-inflammatory effects of compounds 1 and 4 were evaluated in LPS-activated RAW 264.7 macrophages.Compound 4 decreased LPS-induced releases of IL-1βand IL-17αin RAW264.7 cells in a dose-dependent manner.Further mechanistic study revealed that 4 suppressed the phosphorylation of IκBαand p65 subunit to regulate the NF-κB signaling pathway.