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生jiang 汤治疗急性胰腺炎多器官损伤的药代动力学和药效学研究。

Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury.

机构信息

Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.

Department of Traditional Chinese Medicine, Wuhan Union Hospital, Wuhan 430000, Hubei Province, China.

出版信息

World J Gastroenterol. 2017 Dec 14;23(46):8169-8181. doi: 10.3748/wjg.v23.i46.8169.

Abstract

AIM

To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction (SJD) in rats with acute pancreatitis (AP) for protecting against multiple organ injury.

METHODS

An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group (CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD (CG + SJD) and a model group treated with SJD (MG + SJD), both of which were orally administered with SJD (5 g/kg) 2 h after surgery. Blood samples were collected the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male Sprague-Dawley rats were randomly divided into a CG, an AP model group (MG), and an SJD treated AP group (SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.

RESULTS

The MG + SJD displayed significantly shorter mean residence time (MRT) and higher clearance (CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T and a lower area under curve (AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α levels in the MG were higher than those in the CG ( < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG ( < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG ( < 0.05).

CONCLUSION

AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP regulating pro- and anti- inflammatory responses, which might guide the clinical application of SJD for AP treatment.

摘要

目的

探讨生jiang 汤(SJD)对急性胰腺炎(AP)大鼠多器官损伤保护作用的药代动力学和药效学。

方法

通过逆行灌注 3.5%牛磺胆酸钠至胆胰管建立 AP 模型,对照组(CG)给予 0.9%氯化钠代替。将 12 只雄性 Sprague-Dawley 大鼠随机分为 CG 加 SJD(CG+SJD)组和模型组加 SJD(MG+SJD)组,术后 2 小时分别给予 SJD(5g/kg)口服。单次给药后,从尾静脉采集血样,分别在 10、20、40 分钟和 1、2、3、4、6、8、12 小时,采用高效液相色谱-串联质谱法检测其主要成分。比较药代动力学参数。在药效学实验中,将 18 只雄性 Sprague-Dawley 大鼠随机分为 CG、AP 模型组(MG)和 SJD 治疗 AP 组(SJDG)。检测血清淀粉酶、脂肪酶和炎症细胞因子,采集心、肺、肝、脾、胰、肾和肠组织进行病理检查。

结果

MG+SJD 组大黄素和芦荟大黄素的平均驻留时间(MRT)明显缩短,清除率(CL)明显升高;芦荟大黄素的达峰时间(T)和 a 明显缩短,曲线下面积(AUC)明显降低;大黄酸的 AUC 明显升高,CL 明显降低;大黄酚的 MRT 明显延长,CL 明显降低,与 CG+SJD 相比。在药效学实验中,MG 组的淀粉酶、白细胞介素(IL)-6、IL-10 和肿瘤坏死因子(TNF)-α水平均高于 CG(<0.05)。经中药汤治疗后,SJDG 组的 IL-10 高于 MG,TNF-α 低于 MG(<0.05)。MG 组的病理评分最高,SJDG 组肺、胰腺、肾脏和肠道的病理评分明显低于 MG(<0.05)。

结论

AP 可能对大鼠生 Jiang 汤主要成分的药代动力学产生不同的影响。SJD 可能通过调节促炎和抗炎反应,减轻 AP 大鼠肺、胰腺、肾脏和肠道的病理损伤,这可能为 SJD 治疗 AP 的临床应用提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531d/5739923/34ff82bb5098/WJG-23-8169-g001.jpg

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