目的:评价鞘内注射特异性真核翻译起始因子2α (eIF2α)去磷酸化抑制剂(Salubrinal)对大鼠神经病理性痛的影响。方法:SPF级健康雄性SD大鼠45只，8～10周龄，体重220～280 g。采用随机数字表法分为5组( n＝9)：假手术组(Sham组)、神经病理性痛组(NP组)和不同剂量Salubrinal组(S 1组、S 2组、S 3组)。采用坐骨神经慢性缩窄损伤(CCI)法制备神经病理性痛模型。于CCI术后第4天行为学测试结束后鞘内注射37.5 μmol Salubrinal 10 μl(S 1组)、15 μl(S 2组)、20 μl(S 3组)，Sham组和NP注射5% DMSO＋生理盐水20 μl，连续给药10 d，1次/d。于CCI术前1 d、术后1、3、5、7、10和14 d(鞘内给药后1 h)时测定术侧足机械缩足反应阈(MWT)和热缩足潜伏期(TWL)。于CCI术后第14天行为学测试结束后，处死大鼠，取背根神经节组织，采用Western blot法检测BIP、eIF2α、p-eIF2α表达水平，免疫荧光法检测BIP、p-eIF2α表达水平，HE染色观察神经元形态变化。 结果:与Sham组比较，NP组CCI术后各时点MWT降低，TWL缩短，BIP和p-eIF2α表达上调，p-eIF2α/eIF2α比值升高( P<0.05)。与NP组比较，S 1组p-eIF2α表达下调，p-eIF2α/eIF2α比值降低( P<0.05)，各时点MWT和TWL差异无统计学意义( P>0.05)，S 2组和S 3组CCI术后5～14 d MWT升高，TWL延长，BIP和p-eIF2α表达下调，p-eIF2α/eIF2α比值降低( P<0.05)，DRG神经元形态结构损伤均有不同程度的改善。 结论:鞘内注射Salubrinal可能通过抑制背根神经节神经元内质网应激，减轻大鼠神经病理性痛。

OBJECTIVE:To study the absorption and biotransformation of liquiritin,cinnamic acid,paeoniflorin,and glycyrrhizic acid in the Guizhi decoction (GZD) in the gastrointestinal tracts of rats.METHODS:A simple and reliable high-performance liquid chromatography method was established and validated for the analysis of the four components of GZD simultaneously in the gastrointestinal tracts of rats.Rats were randomly divided into in situ gastrointestinal loop model,in vitro anaerobic culture model,and blank control groups.All rats were fasted for 12 h and anesthetized using 20％ urethane.Subsequently,the abdominal cavity of each rat was opened,and the stomach,duodenum,jejunum,ileum,cecum,and colon were ligated.For the in situ gastrointestinal loop model group,2.5 mL of GZD (1.0 g crude drug/mL,37 ℃)were injected into the gastrointestinal tract.The abdominal incision was covered with warm,wet cotton,and animals were maintained at 25 ℃.Then,we collected the gastrointestinal tract content after 1.5 h.For the in vitro anaerobic culture model group,the gastrointestinal tract contents of rats were collected and then cultured in 2.5 mL of GZD in an anaerobic environment at 25 ℃ for 24 h.For the blank control group,rats received the same volume of a normal saline solution instead of GZD.High performance liquid chromatography was used to detect the liquiritin,cinnamic acid,paeoniflorin,and glycyrrhizic acid concentrations in each group and calculate the absorption and biotransformation rates of each ingredient.RESULTS:Cinnamic acid (low polarity) was more easily absorbed by each gastrointestinal part than the higher-polarity glycosides.However,the absorption rate in the cecum was higher than that in other parts.The four compounds,cinnamic acid,liquiritin,paeoniflorin,and glycyrrhizic acid,were transformed completely within 24 h in the cecum and colon,whereas they were hardly transformed in the stomach,excluding glycyrrhizic acid.In addition,all ingredients had higher biotransformation rates in the distal small intestine than that in the proximal small intestine.CONCLUSION:Although a portion of the glycosides in GZD was directly absorbed as the prototype forms in the gastrointestinal tract,they were primarily metabolized and transformed into their corresponding metabolites by intestinal flora near the distal small intestine before their absorption.