DA-9701对链脲佐菌素诱导的糖尿病小鼠胃肠动力的影响。

Effect of DA-9701 on the Gastrointestinal Motility in the Streptozotocin-Induced Diabetic Mice.

作者信息

Ha Changyoon, Kim Heejin, Cha Rari, Lee Jaemin, Lee Sangsoo, Ryu Jung-Hwa, Kim Hyunjin, Lee Ok-Jae

机构信息

Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju 52727, Korea.

Division of Gastroenterology, Gyeongsang National University Hospital, Jinju 52727, Korea.

出版信息

J Clin Med. 2021 Nov 13;10(22):5282. doi: 10.3390/jcm10225282.

DOI:10.3390/jcm10225282

PMID:34830563

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8623860/

Abstract

BACKGROUND

Compared to the general population, diabetic patients experience more frequent episodes of gastrointestinal (GI) motility dysfunction, owing to the disruption of functional innervations. DA-9701 is a new prokinetic agent formulated from the extracts of semen and tuber.

AIM

To investigate the effect of DA-9701 on GI motility in an animal model of streptozotocin (STZ)-induced diabetes.

METHODS

Diabetes was induced in mice by intraperitoneal injection of STZ (40 mg/kg of body weight in 0.1 M citrate buffer) for 3 days. Diabetic mice were divided into four groups and administered DA-9701 in different doses (1, 3, and 10 mg/kg) or placebo for 2 weeks. Intestinal transit was assessed using charcoal meal movement. GI isometric contraction was measured by applying an isometric force transducer on a circular muscle strip of the antrum, ileum, and proximal colon of sacrificed mice. Gastric emptying rate was evaluated by measuring the dye percentage remaining in the stomach relative to the total dye amount recovered in a standardization group of mice.

RESULTS

Body weight and antral and small intestinal motility were less in diabetic mice than in control mice, and colonic motility was similar in both. DA-9701 showed a dose-dependent increase in the amplitude of spontaneous phasic contractions in the antrum, ileum, and colon in diabetic mice without influencing body weight or blood glucose levels. The degree of improvement was comparable between diabetic and control mice. Intestinal transit was significantly more delayed in diabetic mice than in controls (43 ± 7% vs. 67 ± 8%, < 0.05); however, DA-9701 restored the delayed intestinal transit more effectively compared to placebo (75% vs. 50%). The gastric emptying rate was significantly more delayed in diabetic mice than in controls (43 ± 10% vs. 62 ± 12%, < 0.05), and was improved by DA-9701 in a dose-dependent manner (50%, 55%, and 60% in mice treated with 1, 3, and 10 mg/kg of DA-9701, respectively, vs. 43% in placebo-treated and 60% in control mice).

CONCLUSIONS

DA-9701 improved GI contractility without affecting blood sugar and body weight in diabetic mice. DA-9701 could improve the decreased GI motility and clinical symptoms in progressive diabetic patients.

摘要

背景

与普通人群相比，糖尿病患者由于功能性神经支配的破坏，胃肠道（GI）动力功能障碍发作更为频繁。DA - 9701是一种由精液和块茎提取物制成的新型促动力剂。

目的

研究DA - 9701对链脲佐菌素（STZ）诱导的糖尿病动物模型胃肠道动力的影响。

方法

通过腹腔注射STZ（在0.1 M柠檬酸盐缓冲液中，40 mg/kg体重）连续3天诱导小鼠糖尿病。将糖尿病小鼠分为四组，分别给予不同剂量（1、3和10 mg/kg）的DA - 9701或安慰剂，持续2周。使用炭末移动评估肠道转运。通过将等长力传感器应用于处死小鼠的胃窦、回肠和近端结肠的环形肌条来测量胃肠道等长收缩。通过测量相对于标准化小鼠组中回收的总染料量，胃中剩余染料的百分比来评估胃排空率。

结果

糖尿病小鼠的体重、胃窦和小肠动力低于对照小鼠，结肠动力在两者中相似。DA - 9701使糖尿病小鼠胃窦、回肠和结肠的自发性相性收缩幅度呈剂量依赖性增加，而不影响体重或血糖水平。糖尿病小鼠和对照小鼠的改善程度相当。糖尿病小鼠的肠道转运明显比对照小鼠延迟（43±7%对67±8%，P<0.05）；然而，与安慰剂相比，DA - 9701更有效地恢复了延迟的肠道转运（75%对50%）。糖尿病小鼠的胃排空率明显比对照小鼠延迟（43±10%对62±12%，P<0.05），并且DA - 9701以剂量依赖性方式改善了胃排空率（分别用1、3和10 mg/kg DA - 9701处理的小鼠中胃排空率分别为50%、55%和60%；安慰剂处理的小鼠中为43%，对照小鼠中为60%）。