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. 2017 Jan 4:7:39801.
doi: 10.1038/srep39801.

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation

Jun-Fan Fang  1 , Jian-Qiao Fang  1 , Xiao-Mei Shao  1 , Jun-Ying Du  1 , Yi Liang  1 , Wen Wang  1 , Zhe Liu  1
Affiliations

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation

Jun-Fan Fang et al. Sci Rep. .

Abstract

Postoperative ileus (POI) after abdominal surgery significantly lowers the life quality of patients and increase hospital costs. However, few treatment strategies have successfully shortened the duration of POI. Electroacupuncture (EA) is a modern way of administering acupuncture and widely used in various gastrointestinal (GI) diseases in the world. Here, we studied the effect of EA on POI and its underlying mechanisms. Intestinal manipulation resulted in significant delays of GI transit, colonic transit and gastric emptying. Surgery also up-regulated c-fos in nucleus of the solitary tract (NTS) and induced inflammation response in the small intestine. Further, operation and inhale anesthesia inhibited NTS neuron excitation duration for the whole observation time. EA administered at ST36 indeed shortened the recovery time of GI and colonic transit, and significantly increased the gastric emptying. EA also significantly activated the NTS neurons after operation. However, there was no anti-inflammation effect of EA during the whole experiment. Finally, atropine blocked the regulatory effect of EA on GI function, when it was injected after surgery, but not before surgery. Thus, the regulatory effect of EA on POI was mainly mediated by exciting NTS neurons to improve the GI tract transit function but not by activating cholinergic anti-inflammatory pathway.

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Figures

Figure 1
Figure 1. Gastrointestinal tract transit after abdomen operation.
Manipulation of the rat intestine leads to a postoperative delay of intestinal transit as measured by the distribution and geometric center (GC) of fluorescent marker and EA partly recovered the gastrointestinal transit at 24 h after operation. The distribution of orally administered FITC-dextran in whole gastrointestinal tract 6 h (A), 12 h (C) and 24 h (E) after operation and the mean GC of fluorescent marker 6 h (B), 12 h (D) and 24 h (F) after surgery. n = 6–8 rats per group and data are means ± SEM. **P < 0.01 versus control group, ΔP < 0.05 versus model group, #P < 0.05 versus EA group.
Figure 2
Figure 2. Colonic transit and gastric emptying after abdomen operation.
Surgery manipulation of the rat small intestine produced a pronounced increase of colonic transit time of a 5-mm stainless steel ball and a significantly increase of gastric retention. EA stimulation at ST36 reversed them. The mean colonic transit time of a stainless steel ball was calculated 6 h, 12 h and 24 h after surgery (A) and the average gastric retention 24 h after operation (B). n = 6–8 rats per group and data are means ± SEM. **P < 0.01 versus control group, ΔΔP < 0.01 versus model group, ##P < 0.01 versus EA group.
Figure 3
Figure 3. c-fos expression in nucleus of solitary tract after abdomen operation.
Manipulation of the gastrointestinal tract promoted the c-fos expression level of bilateral nucleus of solitary tract (NTS), however, EA simulation produced little effect on these change. Immunofluorescence staining of c-fos expression at bilateral NTS from rats that underwent a laparotomy alone (A), a laparotomy with intestinal manipulation (B), a intestinal manipulation with EA stimulation (C) and intestinal manipulation with sham EA stimulation (D) 24 h after operation. The mean number of positive reaction cells of c-fos from NTS 6 h (E), 12 h (F) and 24 h (G) after operation. Scale bar represent 200 μm. n = 6–8 rats per group and data are means ± SEM. **P < 0.01 versus control group.
Figure 4
Figure 4. Nucleus of solitary tract neurons excitation after abdomen operation.
Manipulation of the gastrointestinal tract and the inhaled anesthetized suppressed the NTS neurons excitation till 24 h after operation and EA excited the NTS. The distribution of three types neuron in NTS of four group immediately (A), 6 h (C), 12 h (E) and 24 h (G) after operation and the rate of change of spike frequency of NTS neurons 10 min (B), 6 h (D), 12 h (F) and 24 h (H). Results of three type neurons’ number are presented as count data and results of the rate of change of spike frequency are mean, quartile and standard deviation. **P < 0.01 versus control group, ΔΔP < 0.01 versus model group, ##P < 0.01 versus EA group.
Figure 5
Figure 5. EA excitatory effect on nucleus of solitary tract neurons on normal rats.
EA stimulation excited the NTS neurons when administrated to normal rats. The distribution of three types neuron in NTS of four group 2 min (A), 4 min (C), 6 min (E), 8 min (G) and 10 min (I) after EA stimulation and the rate of change of spike frequency of NTS neurons 2 min (B), 4 min (D), 6 min (F), 8 min (H) and 10 min (J). Results of three type neurons’ number are presented as count data and results of rate of change of spike frequency are mean, quartile and standard deviation. *P < 0.05 versus normal group.
Figure 6
Figure 6. Leukocyte infiltration in intestinal wall after abdomen operation.
Manipulation of the gastrointestinal tract produced a pronounced leukocyte infiltration in intestinal wall from 6 h to 24 h after surgery and EA stimulation had little effect on infiltration. MPO staining of muscle whole mounts from rats that underwent a laparotomy alone (A), a laparotomy with intestinal manipulation (B), an intestinal manipulation with EA stimulation (C) and intestinal manipulation with sham EA stimulation (D) 24 h after operation. The mean number of MPO-positive cells in small intestine 6 h (E), 12 h (F) and 24 h (G) after operation. Scale bar represent 20 μm. n = 6–8 rats per group and data are means ± SEM. **P < 0.01 versus control group.
Figure 7
Figure 7. IL-1β and TNF-α mRNA expression in small intestinal after abdomen operation.
Manipulation of the gastrointestinal tract produced a pronounced IL-1β and TNF-α mRNA expression in small intestinal from 6 h to 24 h after surgery and EA stimulation had little regulation. IL-1β mRNA relative expression level in intestinal wall of four group 6 h (A), 12 h (B) and 24 h (C) after operation. TNF-αmRNA relative expression level in intestinal wall of four group 6 h (D), 12 h (E) and 24 h (F) after operation. n = 6–8 rats per group and data are means ± SEM. **P < 0.01 versus control group.
Figure 8
Figure 8. Atropine inhibit EA’s effect.
EA’s regulatory effect on gastrointestinal transit, colonial transit time and gastro emptying was inhibited by atropine when it was administrated after operation, but not before. The distribution of orally administered FITC-dextran in whole gastrointestinal tract (A) and the mean GC of fluorescent marker (B) 24 h after surgery. The mean colonic transit time (C) and the average gastric retention 24 h after operation (D). n = 6–8 rats per group and data are means ± SEM. ΔP < 0.05, ΔΔP < 0.01 versus model group, &P < 0.05, &&P < 0.01 versus atr + EA group.
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