Yuan Ling, Zhu Lv, Zhang Yumei, Chen Huan, Kang Hongxin, Li Juan, Zhao Xianlin, Wan Meihua, Miao Yifan, Tang Wenfu
Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China.
Chin Med. 2018 Jul 13;13:38. doi: 10.1186/s13020-018-0195-8. eCollection 2018.
The traditional Chinese formula Da-Cheng-Qi-decoction (DCQD) has been used to treat acute pancreatitis for decades. DCQD could ameliorate the disease severity and the complications of organ injuries, including those of the liver and lungs. However, the pharmacological effects in the kidney, a target organ, are still unclear. This study aimed to investigate the herbal tissue pharmacology of DCQD for acute kidney injury (AKI) in rats with severe acute pancreatitis (SAP).
Rats were randomly divided into the sham-operation group (SG), the model group (MG) and the low-, medium- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. Different doses of DCQD were administered to the treatment groups 2 h after the induction of SAP. The major components of DCQD in kidney tissues were detected by HPLC-MS/MS. Inflammatory mediators in the kidney tissues, as well as serum creatinine (Scr), blood urea nitrogen (BUN) and pathologic scores, were also evaluated.
Ten components of DCQD were detected in the kidneys of the treatment groups, and their concentrations increased dose-dependently. Compared with the SG, the levels of inflammatory mediators, Scr, BUN and pathological scores in the MG were obviously increased ( < 0.05). The high dose of DCQD showed a maximal effect in downregulating the pro-inflammatory mediators interleukin-6 (IL)-6 and tumour necrosis factor-α (TNF-α), upregulating anti-inflammatory mediators IL-4 and IL-10 in the kidney and alleviating the pathological damages. DCQD decreased the pancreas and kidney pathological scores of rats with SAP, especially in the HDG ( < 0.05). Compared with the MG, the level of Scr in the HDG was significantly decreased (p < 0.05).
DCQD ameliorated AKI in rats with SAP via regulating the inflammatory response, which might be closely related to the distribution of its components in the kidney.
中药方剂大承气汤（DCQD）已用于治疗急性胰腺炎数十年。DCQD可改善疾病严重程度及器官损伤的并发症，包括肝和肺的损伤。然而，其对靶器官肾脏的药理作用仍不清楚。本研究旨在探讨DCQD对重症急性胰腺炎（SAP）大鼠急性肾损伤（AKI）的中药组织药理学。
将大鼠随机分为假手术组（SG）、模型组（MG）和低、中、高剂量治疗组（分别为LDG、MDG和HDG）。将牛磺胆酸钠（3.5%）逆行灌注到胆胰管中以建立大鼠SAP模型。在诱导SAP 2小时后，给治疗组给予不同剂量的DCQD。通过HPLC-MS/MS检测肾脏组织中DCQD的主要成分。还评估了肾脏组织中的炎症介质以及血清肌酐（Scr）、血尿素氮（BUN）和病理评分。
在治疗组大鼠的肾脏中检测到DCQD的10种成分，其浓度呈剂量依赖性增加。与SG相比，MG中炎症介质、Scr、BUN水平和病理评分明显升高（<0.05）。高剂量DCQD在下调肾脏中促炎介质白细胞介素-6（IL）-6和肿瘤坏死因子-α（TNF-α）、上调抗炎介质IL-4和IL-10以及减轻病理损伤方面显示出最大效果。DCQD降低了SAP大鼠的胰腺和肾脏病理评分，尤其是在HDG中（<0.05）。与MG相比，HDG中Scr水平显著降低（p<0.05）。
DCQD通过调节炎症反应改善了SAP大鼠的AKI，这可能与其成分在肾脏中的分布密切相关。
