Abstract
The aim of this study was to explore the optimal therapeutic dose and time window of picroside II for treating cerebral ischemic injury in rats according to the orthogonal test. The middle cerebral artery occlusion (MCAO) models were established by intraluminally inserting a thread into middle cerebral artery (MCA) from left external carotid artery (ECA). The successful rat models were randomly divided into 16 groups according to the orthogonal layout of [L16(45)] and treated by injecting picroside II intraperitoneally with different doses at various times. The neurological behavioral function was evaluated by Bederson’s test and the cerebral infarction volume was measured by tetrazolium chloride (TTC) staining. The expressions of neuron specific enolase (NSE) and neuroglial mark-protein S-100 were determined by immunohistochemisty assay. The results indicated that the optimal compositions of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury were ischemia 1.5 h with 20 mg/kg body weight according to Bederson’s test, 1.0 h with 20 mg/kg body weight according to cerebral infarction volume, 1.5 h with 20 mg/kg body weight according to the expressions of NSE and S-100 respectively. Based on the principle of the minimization of medication dose and maximization of therapeutic time window, the optimal composition of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury should be achieved by injecting picroside II intraperitoneally with 20 mg/kg body weight at ischemia 1.5 h.
Highlights
Cerebral ischemic reperfusion injury is a pathological process resulting from many factors, such as excitatory amino acids releasing, oxidative stress, calcium ion overloading, inflammatory reaction, apoptosis, etc. [1,2,3]
All data are analyzed by the statistical mean of two-way ANOVA and LSD value, the analytic results showed that there was no significant differences between administering drug at ischemia 1 h (A1) and 1.5 h (A2), and between administering drug at ischemia 2 h (A3) and 2.5 h (A4), P > 0.05
All data are analyzed by the statistical mean of two-way ANOVA and LSD value, it is concluded that there was a significant deviation of neuron specific enolase (NSE) expression between each medication time (P < 0.05), while no significant deviation between 20 mg/kg (B3) and 40 mg/kg (B4) (P > 0.05), but there was significant deviation between the rest therapeutic dose combination (P < 0.05)
Summary
Cerebral ischemic reperfusion injury is a pathological process resulting from many factors, such as excitatory amino acids releasing, oxidative stress, calcium ion overloading, inflammatory reaction, apoptosis, etc. [1,2,3]. The authors’ former experiments indicated that picroside II could reduce the degradation of the substrate, poly ADP-ribose polymerase (PARP) with catalytic activity, by inhibiting the expression toll-like receptor 4 (TLR4), nuclear transcription factor κB (NFκB), tumor necrotic factor α (TNFα) and Capase-3, and make PARP to utilize the remanent energy in the cells of ischemic penumbra to repair the nerve cells which have the reversibility of refreshing, so that to inhibit the ischemic injury leading to the apoptosis [16,17,18,19,20,21,22,23] In these experiments, the rats were treated by injecting picroside II with a simple dose (20 mg/kg) at a simple time after ischemia (2 h) from tail vein. The authors aimed to explore the optimal therapeutic dose and time window of picroside II injecting intraperitoneally in cerebral ischemic injury in rats according to the design principle of orthogonal test
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