| Objective:To explore the effect of Sufentanil and Ketorolac Tromethamine on gastrointestinal functions of mice after abdominal operation and its mechanism.Methods:(1)Forty Kunming male mice(6-7weeks old,28-35g in weight)were randomly divided into 4 groups:Control group(Group C);Operation model group(Group P):abdominal surgery;Operation + Sufentanil group(Group surgery +SF):Abdominal surgery after administration of Sufentanil 48 hours postoperative analgesia;Operation+ Sufentanil + Ketorolac Tromethamine group(Group surgery +SF+D):Abdominal surgery after administration of Sufentanil and Ketorolac tromethamine 48 hours postoperative analgesia,each with 10 mice.Ink emptying mensuration was adopted to measure the small intestine propelling rates of the 4 groups of mice after the analgesia which lasted 48h.(2)Fifty-eight hours after surgery,tissue homogenate of small intestine was extracted to measure the factor value of MPO.Fifty-eight hours after surgery,mice were sacrificed after eye blood collection,contents of TNF-α,IL-1β and IL-10 in mice serum was measured by ELISA,then flow Cytometry was used to detect the percent content of CD4+ CD25+ Foxp3+ Treg cells in spleen cells of mice.(3)Under LPS(1 μg\ml)presence and absence conditions,Sufentanil(5 ng\ml)and Sufentanil(5 ng\ml)+ Ketorolac Tromethamine(5 mg\nl)were cultured with macrophage in continuous 6h.Then RT-PCR was used to measure the mRNA expression of TNF-α,IL-6 and IL-1β in different treatment groups.After a continuous 48h culture with macrophage,the supernatants were collected and measured by ELISA to determine the factor contents of TNF-α,IL-1β and IL-10.Results:(1)Compared with Group C,small intestine propelling rates of other groups were all declined,with significant difference(p<0.01)5 especially for Group P.Compared with Group P,the small intestine propelling rate of Group surgery +SF(0.375±0.04 vs 0.349±0.08)was declined slightly and had no significant difference;while the small intestine propelling rate of Group surgery +SF+D(0.375±0.04 vs 0.438±0.07)was increased and had significant difference(p<0.01)(2)Compared with Group C,the MPO activities of other groups were all significantly increased,with significant difference(p<0.01);Compared with Group P,the MPO activity in tissue homogenate of small intestine of Group surgery +SF was declined(7.03±0.53 vs 6.53±0.47),with differential change(p<0.05);the MPO activity of Group surgery +SF+D(7.03±0.53 vs 4.56±0.61)was significantly declined,with significant difference(p<0.01).(3)① Compared with Group C,the expressions of IL-1β and TNF-α of Group P(2.18±0.86 pg\ml vs 15.17± 1.67 pg\ml、8.01 ±2.51 pg\ml vs 55.58±4.14 pg\ml)was increased(p<0.01).Compared with Group P(15.17±1.67 pg\ml、55.58±4.14 pg\ml),contents of IL-1β and TNF-α of Group surgery+ SF(12.73±1.27 pg\ml、42.01±5.81 pg\ml)were declined,with differential change(p<0.05,P<0.01),and the contents of IL-1β and TNF-a of Group surgery +SF+D(8.73±1.15 pg\ml、31.85±2.92 pg\ml)were significantly declined,with significant difference(p<0.01).② Compared with Group C(109.4± 13.09 pg\ml),IL-10 contents in serum of Group P(165.30±10.34 pg\ml),Group surgery+SF(168.39±11.35 pg\ml)and Group surgery+SF+D(203.58±15.98 pg\ml)were all increased(p<0.05,p<0.01).(4)Compared with Group C(4.418±0.237),the percent content of CD4+CD25+Foxp3+Treg cells in mice spleen cells of Group P(4.876±0.181)、Group surgery +SF(4.924±0.198)and Group surgery +SF+D(5.464±0.413)were all increased(p<0.05,p<0.01).(5)A six hours stimulation of Sufentanil on LPS had inhibitory effect(p<0.05,p<0.05,p<0.01)to the mRNA expressions of TNF-a,IL-6 and IL-1β in mouse peritoneal macrophage(MPM).A six hours stimulation of Sufentanil +Ketorolac Tromethamine on lipopolysaccharide had significant inhibitory effect(p<0.01)to the mRNA expressions of TNF-α,IL-6 and IL-1β in MPM.A forty-eight hours stimulation of Sufentanil on LPS had inhibitory effect(p<0.05)to the secretions of proinflammat-ory factors TNF-αaand IL-1β in MPM,and had acceleration effect(p<0.05,p<0.01).A forty-eight hours stimulation of Sufentanil + Ketorolac Tromethamine on LPS had significant inhibitory effect(p<0.01)to the secretions of factors TNF-α and IL-1β in MPM,and had significant acceleration effect(p<0.01)to the secretion of anti-inflammatory factor IL-10.Conclusion:(1)Using Sufentanil and Ketorolac Tromethamine combined for postoperative analgesia can improve the function of postoperative gastrointestinal peristalsis.The mechanism may be related to down-regulating the expression of proinflammatory cytokines TNF-α,IL-6 and IL-1β up-regulating the expression of anti-inflammatory factor IL-10.(2)Using Sufentanil and Ketorolac Tromethamine combined for postoperative analgesia,with anti-inflammatory effects.The mechanism may be to improve the peripheral immune system CD4 + CD25 + Foxp3 + regulatory T cells and reduce MPO,thereby inhibiting the inflammatory response. |
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