1.Impact of geniposide on lung injury in rats with acute respiratory distress syndrome by regulating AMPK/SIRT1/NF-κB signaling pathway
Liyan SUN ; Haiyan ZHANG ; Zeru LIU ; Qingwei YIN
Chinese Journal of Immunology 2024;40(6):1142-1146,1152
Objective:To investigate the impact of geniposide(GE)on lung injury in rats with acute respiratory distress syn-drome(ARDS)by regulating AMP-activated protein kinase(AMPK)/silencing information regulator 1(SIRT1)/nuclear factor κB(NF-κB)signaling pathway.Methods:The ARDS rat model was established by tracheal instillation of lipopolysaccharide(LPS).Fifty rats after modeling were randomly group into ARDS group,GE low-dose(GE-L,12.5 mg/kg GE)group,GE medium-dose(GE-M,25 mg/kg GE)group,GE high-dose group(GE-H,50 mg/kg GE)group and GE-H+Compound C(AMPK inhibitor,50 mg/kg GE+250 μg/kg Compound C)group,another 10 normal rats were used as the control group.After the intervention,the bronchoalveolar la-vage fluid(BALF)and lung tissue of the rats in each group were taken out,respectively,and the ratio of lung wet to dry weight(W/D)was detected;ELISA was used to detect the levels of inflammatory factors IL-6,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)in BALF;the positive expressions of vascular cell adhesion factor(VCAM-1)and vascular endothelial cell growth factor(VEGF)in lung tissue were detected by immunohistochemistry;HE staining was used to observe the pathological changes of lung tissue;Western blot was used to detect the expression levels of AMPK/SIRT1/NF-κB pathway proteins in lung tissue.Results:The levels of W/D,IFN-γ,IL-6,TNF-α,p-NF-κB p65/NF-κB p65 and VCAM-1 in ARDS group were significantly higher than those in control group,the expressions of p-AMPK/AMPK,SIRT1 and VEGF were significantly decreased(P<0.05);after different doses of GE treatment,the levels of W/D,IFN-γ,IL-6,TNF-α,and the expressions of p-NF-κB p65/NF-κB p65 and VCAM-1 were gradually decreased compared with those in ARDS group;the expressions of p-AMPK/AMPK,SIRT1 and VEGF increased gradually(P<0.05);Compound C reversed the protective effect of GE-H on ARDS rats(P<0.05).Conclusion:GE can improve lung injury in ARDS rats and reduce levels of inflammatory factors,which may be related to activation of AMPK/SIRT1/NF-κB signaling pathway.
2.Role of mGluR5 in laterocapcular division of central nucleus of amygdala in fentanyl-induced hyperalgesia in rats.
Journal of Central South University(Medical Sciences) 2019;44(4):364-369
To investigate the role of metabotropic glutamate receptor 5 (mGluR5) in laterocapcular division of the central nucleus of amygdala (CeLC) in fentanyl-induced hyperalgesia in rats.
Methods: A total of 12 Sprague-Dawley male rats (60-100 g) were randomly divided into a normal group 1 (n=6) and an opioid-induced hyperalgesia (OIH) group 1 (n=6). The OIH group 1 was injected with fentanyl through the lower neck skin to build OIH model, and the normal group 1 was given the same volume of saline. After 6.5 h, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested to verify the success of the induction of OIH. Then rats were sacrificed and the right CeLC tissue were taken for detection of the mGluR5 by Western blotting. Forty SD male rats were randomly divided into 4 groups (n=10 each): an OIH+DMSO, an OIH+MTEP (3.0 μg), an OIH+MTEP (7.5 μg) and an OIH+MTEP (15.0 μg) group. MTEP was a selective antagonist of mGluR5. Catheterization in the right CeLC was first performed. After one-week recovery, OIH was induced. Then 0.5 μL DMSO, MTEP 3.0 μg, MTEP 7.5 μg and MTEP 15.0 μg were administrated through the CeLC catheter accordingly. PWMT and PWTL were tested at pre-OIH, 6 h after OIH and post-drug. Then the expression levels of mGluR5 of CeLC tissue were analyzed by Western blotting. Another 8 SD male rats were randomly divided into a normal group 2 and an OIH group 2 (n=4 each). The rats were induced OIH by injecting of fentanyl while rats in the normal group 2 were injected with same volume of saline. The miniature excitatory postsynaptic currents (mEPSCs) of the 2 groups' neurons in the right CeLC region were recorded by whole cell voltage-clamp before and after the administration of MTEP in brain slice.
Results: Compared with the normal group 1, the PWTL and PWMT were significantly decreased and the expression of mGluR5 was apparently increased in the OIH group 1 (P<0.05). The PWMT and PWTL were significantly decreased in each group and indicated success of OIH model (P<0.05). The expression of mGluR5 in the CeLC was increased. MTEP reversed these changes in a dose-dependent way (P<0.05). Compared with the normal group 2, the amplitude and frequency of mEPSCs in the OIH group 2 were significantly increased (P<0.05) and they were reversed by MTEP (P<0.05).
Conclusion: mGluR5 in the CeLC may be involved in the maintenance of OIH. Inhibition of the activity of mGluR5 in the CeLC may alleviate the symptoms of fentanyl-induced hyperalgesia.
Animals
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Central Amygdaloid Nucleus
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Fentanyl
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Hyperalgesia
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Male
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Rats
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Rats, Sprague-Dawley
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Receptor, Metabotropic Glutamate 5
3.Visualization of nasal powder distribution using biomimetic human nasal cavity model.
Jiawen SU ; Yan LIU ; Hongyu SUN ; Abid NAEEM ; Huipeng XU ; Yue QU ; Caifen WANG ; Zeru LI ; Jianhua LU ; Lulu WANG ; Xiaofeng WANG ; Jie WU ; Lixin SUN ; Jiwen ZHANG ; Zhigang WANG ; Rui YANG ; Li WU
Acta Pharmaceutica Sinica B 2024;14(1):392-404
Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.
4.Surgical Efficacy and Quality of Life of Total Pancreatectomy versus Pancreatico- duodenectomy for Pancreatic Cancer: A Retrospective Cohort Study Based on Propensity Score Matching
Tianyu LI ; Bangbo ZHAO ; Zeru LI ; Yutong ZHAO ; Xianlin HAN ; Taiping ZHANG ; Menghua DAI ; Junchao GUO ; Weibin WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(4):807-818
To investigate the differences in postoperative short-term complications and long-term prognosis of pancreatic cancer(PC) patients after total pancreatectomy(TP) and pancreaticoduodenectomy(PD). Clinical data of PC patients who underwent TP from January 2016 to December 2021(TP group) and PD from January 2019 to December 2021(PD group) at Peking Union Medical College Hospital were retrospectively collected. Patients in the PD group were divided into the pancreatic fistula(PF) high-risk PD group and the recurrence high-risk PD group according to risk factors. After propensity score matching, the differences in postoperative short-term surgical efficacy indicators(postoperative complication rate, 30 d mortality rate, length of hospital stay, etc.), long-term surgical efficacy indicators(overall survival), and quality of life were compared between the TP group and the PF high-risk PD group or the recurrence high-risk PD group. A total of 32 patients in the TP group and 114 patients in the PD group(99 patients in the PF high-risk PD group and 15 patients in the recurrence high-risk PD group) meeting the inclusion and exclusion criteria were enrolled.(1)TP group and PF high-risk PD group: after propensity score matching, 29 patients in the TP group and 56 patients in the PF high-risk PD group were finally included. There was no PF in the TP group, and the rate of PF in the PF high-risk PD group was 19.64%( For PC patients at high risk of PF, TP can achieve short-term surgical outcomes and long-term quality of life comparable to PD with no burden of postoperative pancreatic fistula. For patients with high-risk recurrence, TP can significantly prolong the survival of PC patients while ensuring surgical safety.