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Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.
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AIM: To verify the role of tetramethylpyrazine (TMP) in intestinal ischemia-reperfusion (I/ R) injury and its relationship with pyroptosis. METHODS: Thirty-six healthy SPF male C57BL / 6 mice, 8-12 weeks old, weighing 20-25 g, were divided into six groups randomized by table of random number (n = 6/group): Sham group (S1 group)Ischemia/reperfusion group (I/R1 group), I/R + TMP treatment group: 15 mg/kg (T15 group), 30 mg/kg (T30 group), 60 mg/kg (T60-1 group), 120 mg/kg (T120 group). In experiment 2, thirty healthy SPF male C57BL/6 mice were divided into five groups (n = 6/group): Sham group (S2 group), I/R group (I/ R2 group), I/R + dimethyl sulphoxide (DMSO) group (DMSO group), I/R + TMP (60 mg/kg) group (T60-2 group), and I/R + DMSO + TMP (60 mg/kg) + Nigericin sodium salt (NSS) group (T60+NSS group). I/R-induced intestinal injury was established by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion, while the sham group mice underwent isolation of superior mesenteric artery without clamping. An NLRP3 agonist NSS was dissolved in DMSO, was intraperitoneally injected (4 mg/kg) 60 minutes before ischemia. And DMSO group mice were intraperitoneally administered with corresponding DMSO. Different TMP dosage groups and T60+NSS group mice were intraperitoneally administered with TMP 30 minutes before ischemia. IL-1β and IL-18 concentrations in the intestine were measured at 120 minutes after reperfusion by ELISA. The pathological changes of the sections were observed by optical microscope, and the intestinal mucosal injury was evaluated by Chiu's score grading. Western blot was used to detect NLRP3, Caspase-1, and GSDMD in intestinal tissue. RESULTS: Statistically significant increase of Chiu's score, IL-1β, IL-18 concentrations in the I/R1 group were found as compared with S1 group (P<0.05). And compared with I / R1 group, Chiu's score and IL-1β, IL-18 concentrations in the T60-1, T120 groups were reduced (P<0.05). Moreover, Chiu's score in the T120 group was lower than that in the T60 group (P<0.05). We found a statistically significant increase of Chiu's score and IL-1β, IL-18 concentrations and the expression of NLRP3, GSDMD, caspase-1 in the I/R group (P<0.05) as compared with S2 group. Compared with I / R2 group, Chiu's score, IL-1β, IL-18 concentrations and NLRP3, GSDMD, caspase-1 expression in the T60-2 group was reduced (P<0.05). Compared with T60-2 group, Chiu's score, IL-1β, IL-18 concentrations and NLRP3, GSDMD, caspase-1 expression in the T60 + NSS group were upregulated (P<0.05). CONCLUSION: The protective effect of TMP against intestinal I / R injury was dose-dependent. And TMP can decrease pyroptosis mainly by inhibiting the activation of the NLRP3 inflammasome.
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AIM: To explore schisandrin B (Sch B) pretreatment reduces intestinal ischemia reperfusion injury (IIRI) through inhibiting apoptosis by activation of Nrf2/HO-1 signing pathway in mice by network pharmacology and in vivo experiment. METHODS: (1) The targets of Sch B and IIRI were searched from online databases, Drawing Venn diagram to obtain the common target of them. Cytoscape software was imported to construct the protein-protein interaction (PPI) network to establish the "Drugs-Disease-core target gene" network. The mechanism of Sch B against IIRI was predicted through GO and KEGG enrichment analysis. (2) Thirty-six C57BL/6J mice were randomly divided into six groups (n = 6). The model of IIRI was established in four groups except the sham operation group. Three of the groups were pretreated with Sch B, Nrf2 inhibitor ML385, and Sch B + ML385, respectively. After the experiment, intestinal tissue samples were taken for HE staining, Chiu ' s score, apoptosis staining, immunohistochemistry (IHC), and immunoblotting (Western blot). RESULTS: A total of 412 Sch B related tar- gets, 2 166 IIRI related targets and 153 common targets were screened out through network pharmacology. There were 88 "Sch B-IIRI-core target gene" included NFE2L2 (Nrf2), HMOX1 (HO-1), BCL2, CASP3 (caspase 3), and so on. KEGG enrichment analysis screened 163 related pathways, apoptosis pathway ranked high showing that the pathway may play a key role in the treatment of IIRI by Sch B. The animal experiment had shown that Sch B reduced the Chiu's score and apoptotic while upregulating Nrf2, HO-1, Bcl-2 protein expression levels and Bcl-2/Bax, downregulating Bax, and cleaved caspase-3 expression levels, thereby reducing IIRI in mice, and that Nrf2 inhibitor ML385 reversed this process (P < 0.05). CONCLUSION: This study reveals that Sch B has the characteristics of multi-target and multi-pathway in the reduction of IIRI, and Sch B can reduce IIRI through inhibiting apoptosis by activation of Nrf2/ HO-1 pathway.
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Objective:To evaluate the role of histone deacetylase (HDAC) in sodium butyrate-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with oxidative stress and cell apoptosis.Methods:Twenty-four SPF healthy male C57BL mice, aged 6-8 weeks, weighing 22-25 g, were divided into 4 groups ( n=6 each) according to the random number table method: sham operation group (S group), intestinal I/R group (IR group), intestinal I/R+ sodium butyrate group (IN group) and intestinal I/R+ ITSA-1+ sodium butyrate group (INI group). In IR, IN and INI groups, the superior mesenteric artery was clamped for 45 min, followed by reperfusion for 2 h to prepare the model of intestinal I/R injury, while the superior mesenteric artery was only isolated without ligation in S group.One week before preparation of the model, sodium butyrate 500 mg/kg was intragastrically administered once a day in IN group and INI group, the HDAC activator ITSA-1 0.5 mg/kg was intraperitoneally injected three times a week in INI group, and the equal volume of normal saline was given instead in the other groups.The mice were sacrificed at 2 h of reperfusion and small intestinal tissues were obtained for microscopic examination of the pathological changes which were assessed using Chiu′s score and for determination of the content of MDA (by enzyme-linked immunosorbent assay) and expression of cleaved caspase-3 (by Western blot). Results:Compared with S group, Chiu′s score was significantly increased, and the expression of cleaved caspase-3 was up-regulated in IR, IN and INI groups, the content of MDA in small intestinal tissues was significantly increased in IR and INI groups ( P<0.05). Compared with IR group, Chiu′s score was significantly decreased in IN and INI groups, and the content of MDA was significantly decreased, and the expression of cleaved caspase-3 was down-regulated in IN group ( P<0.05). Compared with IN group, Chiu′s score and content of MDA were significantly increased, and the expression of cleaved caspase-3 was up-regulated in INI group ( P<0.05). Conclusions:HDAC is involved in sodium butyrate-induced reduction of intestinal I/R injury in mice, which is related to the inhibition of oxidative stress and cell apoptosis.
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Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in reduction of intestinal ischemia-reperfusion (I/R) injury by sodium butyrate in mice.Methods:Twenty-four SPF healthy adult male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=6 each) by the random number table method: sham operation group (S group), intestinal I/R group (I/R group), intestinal I/R + sodium butyrate group (I/R+ SB group), and intestinal I/R + ITSA-1+ sodium butyrate group (I/R+ I+ SB group). The model of intestinal I/R injury was established by clipping superior mesenteric artery for 45 min followed by 120 min of reperfusion in anesthetized animals.In I/R+ I+ SB group, the HDACs activator ITSA-1 0.5 mg/kg was intraperitoneally injected at 6, 3 and 1 days before ischemia.Sodium butyrate 500 mg/kg was given by intragastric administration every day one week before ischemia in I/R+ SB group and I/R+ I+ SB group, and the equal volume of normal saline was given in S group and I/R group.At 120 min of reperfusion, the mice were sacrificed and their small intestine tissues were obtained.The levels of diamine oxidase (DAO) in serum and intestinal tissues were detected by enzyme-linked immunosorbent assay.The pathological changes of small intestinal tissues were observed with a light microscope, and intestinal damage was assessed and scored according to Chiu.The expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ), P62 and HDAC6 was determined by Western blot.The contents of histone H3 (H3) and acetylated histone H3 (Ac-H3) in small intestinal tissues were determined by enzyme-linked immunosorbent assay. Results:Compared with S group, the Chiu′s score, levels of DAO in serum and small intestinal tissues were significantly increased, the expression of LC3 Ⅱ and HDAC6 was up-regulated, P62 expression was down-regulated, H3 content was increased, and AC-H3 content was decreased in I/R group ( P<0.05). Compared with I/R group, the Chiu′s score, levels of DAO in serum and small intestinal tissues were significantly decreased, the expression of LC3 Ⅱ and HDAC6 was down-regulated, P62 expression was up-regulated, H3 content was decreased, and AC-H3 content was increased in I/R+ SB group ( P<0.05). Compared with I/R+ SB group, the Chiu′s score and levels of DAO in serum and small intestinal tissues were significantly increased, the expression of LC3 Ⅱ and HDAC6 was up-regulated, P62 expression was down-regulated, H3 content was increased, and AC-H3 content was decreased in I/R+ I+ SB group ( P<0.05). Conclusions:Sodium butyrate can alleviate intestinal I/R injury by inhibition of HDAC6 activity in mice, and the mechanism may be related to inhibition of autophagy and promotion of H3 acetylation.
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Objective:To investigate the mechanism of dexmedetomidine preventing sevoflurane-indued neurotoxicity to neonatal mice and the relationship with Tau phosphorylation.Methods:Seventy-two SPF healthy newly born C57BL/6 wild-type mice of both sexes, aged 6 days, were divided into 4 groups ( n=18 each) using a random number table method: normal control group (C group), dexmedetomidine control group (D group), sevoflurane-induced neurotoxicity group (S group), and dexmedetomidine prevention group (SD group). Mice inhaled 2.1%-3.3% sevoflurane 2 h daily on postnatal days 6, 9 and 12, and dexmedetomidine 10 μg/kg was intraperitoneally injected at 30 min before anesthesia in group SD.Six mice were randomly selected after the end of injection, and the hippocampus tissues were removed for determination of the expression of phosphorylated Tau protein (AT8) and Tau46 protein at Tau-PS202 and Tau-PT205 sites by Western blot.The new object recognition test was performed on postnatal days 29-30 (the discrimination ratio of new objects was observed), and the Morris water maze test was performed from postnatal day 31 to 37 (the escape latency and the times of crossing the platform were observed). The hippocampi were harvested under anesthesia to detect the expression of postsynapatic density-95 by Western blot. Results:Compared with group C, the expression of AT8 was significantly up-regulated, the expression of PSD-95 was down-regulated, the number of crossing the platform and new object discrimination ratio were decreased ( P<0.05), and no significant change was found in Tau46 protein expression or escape latency in group S ( P>0.05). There was no significant difference in the indexes mentioned above between group D and group SD ( P>0.05). Compared with group S, the expression of AT8 was significantly down-regulated, the expression of postsynapatic density-95 was up-regulated, the number of crossing the platform and new object discrimination ratio were increased ( P<0.05), and no significant change was found in Tau46 protein expression and escape latency in group SD ( P>0.05). Conclusions:The mechanism of dexmedetomidine preventing sevoflurane-induced neurotoxicity to neonatal mice is related to the inhibition of Tau phosphorylation.
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Butyrate is the main product of colonic and cecal microbiota in the fermentation of dietary fiber and some amino acids, which can reduce intestinal inflammation, regulate the balance of intestinal flora, and improve intestinal mucosal barrier. In recent years, a large number of studies at home and abroad have shown that butyrate plays a role in intestinal diseases such as inflammatory bowel disease, irritable bowel syndrome, intestinal ischemia-reperfusion injury, colorectal cancer and short bowel syndrome. This article reviewed the research progress on role and mechanism of butyrate in intestinal diseases.
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AIM: To observe the effect of paricalcitol on intestinal ischemia-reperfusion injury, and to explore the relationship with HMGB1/TLR4/NF-κB signaling pathway. METHODS: Twenty-four SPF-grade healthy adult male C57BL/6J mice were divided into 4 groups (n=6) by random number table: sham operation group (S group), paricalcitol pretreatment+sham operation group (SP group), intestinal ischemia-reperfusion group (IR group) and paricalcitol ischemic preconditioning group (P group). S group and SP group were separated the superior mesenteric artery, IR group and P group were clamped the superior mesenteric artery for 45 minutes and then followed by reperfusion for 2 hours to establish the intestinal ischemia-reperfusion model; SP group and P group were intraperitoneally injected with 0.3 μg/kg paricalcitol 24 hours before surgery, and the other two groups were given equal volume of normal saline. The mice were sacrificed at 2 h after reperfusion, and the intestinal tissue was obtained 5 cm from the terminal ileum. The pathological results were observed under light microscope. The intestinal mucosal injury was scored according to the Chiu's scoring standard. The intestinal tissue diamine oxidase (DAO) and tumor were detected by ELISA. Necrosis factor α (TNF-α) and interleukin 6 (IL-6) content; Western blot was used to detect the expression levels of HMGB1, TLR4 and NF-κB p65 protein in small intestine tissues.RESULTS: Compared with S group and SP group, Chiu's score was increased, the expression of Dao, TNF-α and IL-6 were increased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein increased significantly in IR group (P< 0.05); Compared with IR group, Chiu's score was decreased, the expression of Dao, TNF-α and IL-6 were decreased, as well as the expression of HMGB1, TLR4 and NF-κB p65 protein decreased significantly in P group (P< 0.05). CONCLUSION: Paricalcitol can alleviate intestinal ischemia-reperfusion injury by inhibiting HMGB1/TLR4/NF-κB signaling pathway and playing an anti-inflammatory role.
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Short-chain fatty acids (SCFAs) are organic acids with no more than 6 carbon atoms produced during the anaerobic fermentation of dietary fiber in the intestinal tract, which can regulate intestinal flora, repair intestinal mucosal barrier, and reduce intestinal injury.Ischemia-reperfusion injury (IRI) is the main cause of various diseases, and the pathological mechanisms involved are intricate, among which inflammation, oxidative stress, apoptosis and autophagy are the most common. According to current studies, SCFAs can affect the occurrence and development of IRI in various organs by regulating different cell signal transduction. In this paper, the role and mechanism of SCFAs in alleviating tissue and organ ischemia-reperfusion injury were preliminarily summarized, providing theoretical reference for clinical prevention and treatment of IRI.
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AIM: To explore the role and mechanism of silent mating type information regulator 2 homolog 3 (SIRT3) in attenuation of intestinal ischemia-reperfusion (I/R) injury by dexmedetomidine in mice. METHODS: Twenty-four healthy male C57BL mice were divided into 4 groups randomly (n=6): sham operation group (Sham group), intestinal ischemia-reperfusion group (I/R group), dexmedetomidine group (Dex group), SIRT3 inhibitor 3-TYP group (3-TYP group). Superior mesenteric artery was clamped for 45 min followed by reperfusion for 2 h to establish intestinal I/R model in I/R group, Dex group, and 3-TYP group. Sham group received sole sham operation. 1 h prior to onset of ischemia, 3-TYP was injected into mice in 3-TYP group intraperitoneally (5 mg/kg, diluted to 0.3 mL), and 0.3 mL normal saline into mice in Dex group intraperitoneally. 30 min prior to onset of ischemia, dexmedetomidine was injected into mice in 3-TYP group and Dex group intraperitoneally (25 μg/kg, diluted to 0.3 mL). 1 h and 30 min prior to onset of ischemia, 0.3 mL normal saline was injected into mice in Sham group and I/R group intraperitoneally, respectively. 2 h of after reperfusion, the mice were sacrificed under anesthesia. Intestinal tissues were took and observed for pathological changes under light microscope after HE staining, and the injury was assessed via the Chiu's score method, and activities of SIRT3 and superoxide dismutase 2 (SOD2) were detected via spectrophotometry, and malondialdehyde (MDA) via spectrophotometry. RESULTS: The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in I/R group, Dex group and 3-TYP group compared to Sham group (P<0.05). The pathological injury was alleviated, and the Chiu's score declined remarkably in Dex group and 3-TYP group compared to I/R group (P<0.05); and the MDA level declined remarkably, while activity level of SIRT3 and SOD2 elevated remarkably in Dex group compared to I/R group (P<0.05); and there was no significant difference both in the activity level of SIRT3 and SOD2 and in the MDA level between 3-TYP group and I/R group. The pathological injury was exacerbated, and the Chiu's score, the MDA level elevated remarkably, while the activity level of SIRT3 and SOD2 declined remarkably in 3-TYP group compared to Dex group (P<0.05). CONCLUSION: SIRT3 and its downstream SOD2 are involved in mediating the effect of attenuation of intestinal ischemia-reperfusion injury through inhibiting oxidative stress response by dexmedetomidine.
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lrisin is an endogenous secreted muscle factor, Which not only plays a certain clinical application value in a variety of metabolic diseases, cardiovascular and cerebrovascular diseases, neurological diseases, tumors and other diseases, but also affects the occurrence and development of organ ischemia/reperfusion injury. ln this paper, the role and mechanism of irisin in organ ischemia/reperfusion injury Were summarized, aiming to provide neW ideas for prevention and treatment of organ ischemia/reperfusion injury.
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Objective:To evaluate the role of peroxidase proliferator-activated receptor γ (PPARγ)/nuclear factor kappa B (NF-κB) signaling pathway in sodium butyrate-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF-grade healthy adult male C57BL/6J mice, aged 7-9 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (IIR group), sodium butyrate group (NaB group) and PPARγ inhibitor GW9662 group (GW9662 group). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.GW9662 2 mg/kg was intraperitoneally injected at 1 h before ischemia in GW9662 group, and sodium butyrate 500 mg/kg was intraperitoneally injected at 30 min before ischemia in NaB and GW9662 groups.Blood samples were obtained via cardiac puncture at 2 h of reperfusion, and the animals were then sacrificed.The intestinal tissues were removed for determination of diamine oxidase (DAO), tumor necrosis factorα (TNF-α) and interleukins 6 (IL-6) concentrations in serum (by enzyme-linked immunosorbent assay) and the expression of PPAR and NF-κB p65 (by Western blot). The damage to intestinal mucous membrane was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score was significantly increased, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were increased, expression of PPARγ was down-regulated, and expression of NF-κB p65 was up-regulated in group IIR ( P<0.05). Compared with group IIR, the Chiu′s score, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were decreased, and expression of PPARγ was up-regulated in group NaB, and expression of NF-κB p65 was up-regulated in NaB and GW9662 groups ( P<0.05). Compared with group NaB, the Chiu′s score, levels of DAO, TNF-α and IL-6 in serum and intestinal tissues were increased, and expression of PPARγ was down-regulated, and expression of NF-κB p65 was up-regulated in group GW9662 ( P<0.05). Conclusion:The mechanism by which sodium butyrate reduces intestinal I/R injury may be related to activating PPARγ/NF-κB signaling pathway and inhibiting inflammatory responses in mice.
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Objective:To evaluate the role of nuclear factor NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in atorvastatin-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divide into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (I/R group), atorvastatin group (ATV group) and atorvastatin+ Nrf2 inhibitor ML385 group (AM group). Intestinal I/R was produced by occlusion of superior mesenteric artery for 45 min followed by reperfusion.In ATV and AM groups, atorvastatin 10 mg/kg was given by gavage for 3 consecutive days daily at 3 day before establishment of the model, while the equal volume of normal saline was given by gavage in S and I/R groups.Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before establishment of the model in group AM.The mice were sacrificed at 2 h of reperfusion, and intestine tissues were obtained for examination of the pathological changes of intestinal tissues (with a light microscope) which were scored according to Chiu, for determination of wet/dry weight ratio (W/D ratio), for detection of the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) (by xanthine oxidase method and thiobarbituric acid condensation method) and for determination of the expression of Nrf2 and HO-1 (by Western blot). Results:Compared with S group, the Chiu score, W/D ratio and MDA content were significantly increased, the activity of SOD was decreased, and the expression of Nrf2 and HO-1 was up-regulated in the other 3 groups ( P<0.05). Compared with the group I/R, the Chiu score, W/D ratio and MDA content were significantly decreased, the SOD activity was increased, and the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological changes were significantly attenuated in group ATV, and no significant change was found in the parameters mentioned above in AM group ( P>0.05). Compared with the group ATV, the Chiu score, W/D ratio and MDA content were significantly increased, the SOD activity was decreased, the expression of Nrf2 and HO-1 was decreased ( P<0.05), and the pathological changes were significantly aggravated in group AM. Conclusion:The mechanism by which atorvastatin reduces intestinal I/R injury is related to activating Nrf2/HO-1 signaling pathway in mice.
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Objective:To investigate the effect of atorvastatin preconditioning on intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) signaling pathway.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), I/R group, atorvastatin preconditioning group (A group), atorvastatin plus PI3K inhibitor LY294002 group (AL group). Atorvastatin 10 mg/kg was given by intragastric gavage for 3 consecutive days in A and AL groups, and in addition LY294002 0.3 mg/kg was intraperitoneally injected at 30 min before the last administration of atorvastatin in AL group.Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 45 min followed by 2 h reperfusion in anesthetized mice.The superior mesenteric artery was only isolated but not clamped in S group.The mice were sacrificed at the end of reperfusion, and small intestinal tissues were taken for determination of the pathological changes with a light microscope after HE staining and for determination of wet to dry weight ratio(W/D ratio) and expression of PI3K, phosphorylated Akt (p-Akt), autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3Ⅰ (LC3Ⅰ) and LC3Ⅱ.The intestinal damage was assessed and scored according to Chiu.The ratio of LC3Ⅱ expression to LC3Ⅰ expression (LC3Ⅱ/LC3Ⅰ) was calculated. Results:Compared with S group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in I/R, A and AL groups ( P<0.05). Compared with I/R group, Chiu′s scores and W/D ratio were significantly decreased, the expression of PI3K and p-Akt was up-regulated, the expression of Beclin-1 was down-regulated, and LC3Ⅱ/LC3Ⅰ ratio was decreased in A group ( P<0.05). Compared with A group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in AL group ( P<0.05). Conclusion:Atorvastatin preconditioning can mitigate intestinal I/R injury in mice, and the mechanism is related to activating PI3K/Akt signaling pathway and inhibiting the level of autophagy.
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microRNA (miRNA) is a class of 19-25 nucleotide highly conserved single-stranded non-coding RNA that is widely found in plants and animals. Their biological effect is to negatively regulate target gene expression at the post-transcriptional level through complementary pairing with mRNA. Intestinal I/R injury is more common in clinical practice, and ischemia-reperfusion will cause intestinal mucosal barrier damage, and it is related to the occurrence, development, and outcome of many clinical diseases. Many studies have shown that the miRNA subtype genes miR-34a-5p, miR-351-5p, miR-682, miR-21, etc. affect the intestinal I/R injury process to some extent by regulating a series of signal transduction. Therefore, revealing the role of miRNA in intestinal I/R injury and providing a new direction for the diagnosis and treatment of I/R.
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AIM: To evaluate the effect of SLC7A11 in dexmedetomidine pretreatment induced reduction of ferroptosis caused by intestinal ischemia-reperfusion (II/R) injury in mice. METHODS: Twenty-four healthy meal SPF C57BL/6J mice, aged 8 weeks, weighing 22-25 g, were randomly divided into Sham operation group (S group), intestinal I/R group (II/R group), dexmedetomidine group (DEX group) and dexmedetomidine plus SLC7A11 inhibitior group (DIKE group), with 6 mice in each group. Intestinal ischemia was induced by occluding the superior mesenteric artery for 45 min followed by 30 min of reperfusion to establish the model of II/R injury. In DEX and DIKE groups, Dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before clamping the superior mesenteric artery. The same amount of normal saline was injected in the S group and the II/R group. In DIKE group, SLC7A11 inhibitior Imidazole ketone erastin 50 mg/kg was intraperitoneally injected at 90 min before ischemia. Mice were sacrificed 30 min after reperfusion, and small intestinal tissues in length 5 cm away from the ileocecal valvum were obtained for microscopic examination of pathological changes of intestinal mucosa and for determination of contents of Fe
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AIM: To observe the anesthetic effect of nalbuphine used in ultrasound-guided transvaginal oocyte retrieval and its effect on embryo quality and pregnancy outcome. METHODS: Four-hundred patients who underwent ultrasound-guided transvaginal oocyte retrieval were randomly divided into two groups (n=200): nalbuphine group (N group) and control group (C group). The patients were in the bladder lithotomy position. Patients in N group were given nalbuphine 0.1 mg/kg intravenously 2 minutes before induction of anesthesia, patients in C group were given normal saline intravenously, and patients in both groups were induced with propofol 1.5 mg/kg. The patients were kept breathing spontaneously, and they were given intravenous injections of propofol (2 mg•kg
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Objective To evaluate the relationship betweenα2 adrenergic receptors and expression of Nav1. 8 in dorsal root ganglion (DRG) neurons, and to illuminate the mechanism of dexmedetomidine-induced reduction of acute visceral pain in rats. Methods Thirty-two clean-grade healthy adult male Spra-gue-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were divided into 4 groups ( n=8 each) using a random number table method: control group ( group C ) , acute visceral pain group ( group VP ) , dexmedetomidine group (group D), and dexmedetomidine plus atipamezole group (group DA). In VP, D and DA groups, 10-3 mmol∕L capsaicin 1. 3 ml was injected into the rectum at a dose of 10-3 mmol∕L to establish the acute visceral pain model, while the equal volume of normal saline was given instead in group C. Atipamezole 1 mg∕kg was subcutaneously injected through the back of the neck at 20 min before establishing the model in group DA. Dexmedetomidine 10μg∕kg was injected through the tail vein at 15 min before establishing the model in D and DA groups, while the equal volume of normal saline was given instead at the correspording time points in C and VP groups. The visceral pain behavior score was recorded at 1 h after establishing the model. The animals were then sacrificed, and DRGs of the lumbar segment (L3-6) were removed for determination of the number of Nav1. 8 positive DRG neurons (by immunohisto-chemistry) and expression of Nav1. 8 mRNA (by quantitative real-time polymerase chain reaction). Results Compared with group C, the visceral behavior scores and the number of Nav 1. 8 positive DRG neurons were significantly increased, and the expression of Nav 1. 8 mRNA was up-regulated in VP, D and DA groups (P<0. 05). Compared with group VP, the visceral behavior score and the number of Nav1. 8 positive DRG neurons were significantly decreased, and the expression of Nav 1. 8 mRNA was down-regulated in D and DA groups (P<0. 05). Compared with group D, the visceral behavior scores and the number of Nav1. 8 positive DRG neurons were significantly increased, and the expression of Nav1. 8 mRNA was up-regulated in group DA ( P<0. 05) . Conclusion The mechanism by which dexmedetomidine reduces acute visceral pain is related to activatingα2 adrenergic receptors and to down-regulating the expression of Nav1. 8 in DRG neu-rons of rats.
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Objective To evaluate the effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway.Methods Forty cleangrade healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 4 groups (n =10 each) using a random number table method:sham operation group (Sham group),abdominal adhesion group (AA group),dexmedetomidine group (DEX group) and dexmedetomidine plus methyllycaconitine group (DEX-M group).The rat model of abdominal adhesions was established by cecal friction method.In Sham group,abdominal cavity was only opened and then sutured.Normal saline 2 ml was injected into the abdominal cavity and tail vein in group AA.In DEX and DEX-M groups,normal saline 2 ml and α7 nicotinic acetylcholine receptor antagonist methyllycaconitine 2.4 μg/g (dissolved in 2 ml normal saline) were injected,respectively,and dexmedetomidine 10μg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected at the same time.The abdominal incision was opened under anesthesia at 7 days after establishing the model to observe the formation of abdominal adhesion,Phillips method was used for scoring,and enzyme-linked immunosorbent assay was used to determine the transforming growth factor-beta1 (TGF-β1) concentrations in ascites and tumor necrosis factor-alpha (TNF-α) concentrations in serum.The rats were then sacrificed,and the caecum tissue and its contralateral peritoneum and adhesion fibrous strips were obtained for examination of the pathological changes with a light microscope.Results Compared with group Sham,the abdominal adhesion score and serum TNF-α concentrations were significantly increased in AA and DEX-M groups,and the TGF-β1 concentration in ascites was significantly increased in AA,DEX and DEX-M groups (P＜0.05).Compared with group AA,the serum TNF-α concentrations and TGF-β1 concentration in ascites were significantly decreased in group DEX-M,and the abdominal adhesion score was significantly decreased (P＜0.05),and the pathological changes of caecum tissue,contralateral peritoneum and adhesion fibrous strips were significantly attenuated in group DEX.Compared with group DEX-M,the serum TNF-o concentrations were significantly increased (P＜0.05),no significant change was found in TGF-1 concentration in ascites (P＞0.05),and the pathological changes of caecum tissue,contralateral peritoneum and adhesion fibrous strips were accentuated in group DEX.Conclusion Intraperitoneally injected dexmedetomidine can mitigate abdominal adhesions,and the mechanism is related to activating cholinergic anti-inflammatory pathway and reducing systemic inflammatory response in rats.
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Objective@#To evaluate the effect of intraperitoneally injected dexmedetomidine on abdominal adhesions in rats and the role of cholinergic anti-inflammatory pathway.@*Methods@#Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 220-250 g, were divided into 4 groups (n = 10 each) using a random number table method: sham operation group (Sham group), abdominal adhesion group (AA group), dexmedetomidine group (DEX group) and dexmedetomidine plus methyllycaconitine group (DEX-M group). The rat model of abdominal adhesions was established by cecal friction method.In Sham group, abdominal cavity was only opened and then sutured.Normal saline 2 ml was injected into the abdominal cavity and tail vein in group AA.In DEX and DEX-M groups, normal saline 2 ml and α7 nicotinic acetylcholine receptor antagonist methyllycaconitine 2.4 μg/g (dissolved in 2 ml normal saline) were injected, respectively, and dexmedetomidine 10 μg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected at the same time.The abdominal incision was opened under anesthesia at 7 days after establishing the model to observe the formation of abdominal adhesion, Phillips method was used for scoring, and enzyme-linked immunosorbent assay was used to determine the transforming growth factor-beta1 (TGF-β1) concentrations in ascites and tumor necrosis factor-alpha (TNF-α) concentrations in serum.The rats were then sacrificed, and the caecum tissue and its contralateral peritoneum and adhesion fibrous strips were obtained for examination of the pathological changes with a light microscope.@*Results@#Compared with group Sham, the abdominal adhesion score and serum TNF-α concentrations were significantly increased in AA and DEX-M groups, and the TGF-β1 concentration in ascites was significantly increased in AA, DEX and DEX-M groups (P<0.05). Compared with group AA, the serum TNF-α concentrations and TGF-β1 concentration in ascites were significantly decreased in group DEX-M, and the abdominal adhesion score was significantly decreased (P<0.05), and the pathological changes of caecum tissue, contralateral peritoneum and adhesion fibrous strips were significantly attenuated in group DEX.Compared with group DEX-M, the serum TNF-α concentrations were significantly increased (P<0.05), no significant change was found in TGF-β1 concentration in ascites (P>0.05), and the pathological changes of caecum tissue, contralateral peritoneum and adhesion fibrous strips were accentuated in group DEX.@*Conclusion@#Intraperitoneally injected dexmedetomidine can mitigate abdominal adhesions, and the mechanism is related to activating cholinergic anti-inflammatory pathway and reducing systemic inflammatory response in rats.