1.Salidroside alleviates PM2.5-induced pulmonary fibrosis through PINK1/Parkin
Ruixi ZHOU ; Wenbo WU ; Limin ZHANG ; Meina WU ; Chen LIU ; Siqi LI ; Xiaohong LI ; Mengxiao LUAN ; Qin WANG ; Li YU ; Yumei LIU ; Wanwei LI
Journal of Environmental and Occupational Medicine 2025;42(10):1240-1246
Background Existing studies have confirmed that fine particulate matter (PM2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg−1 by gavage, n=10), PM2.5 group (intratracheal instillation of PM2.5 5 mg·kg−1 + saline by gavage, n=10), and Sal + PM2.5 group (intratracheal instillation of PM2.5 5 mg·kg−1 +Sal 60 mg·kg−1 by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.
2.Mechanism of mesalazine ameliorating colonic barrier function in mice with ulcerative colitis through Wnt1 pathway
Chinese Journal of Immunology 2024;40(12):2500-2505
Objective:To investigate effect of mesalazine(MSLZ)on improvement of colonic barrier in mice with ulcerative colitis(UC),and its regulatory mechanism on wingless-type mouse mammary tumor virus integration site1(Wnt1)signaling pathway.Methods:C57BL/6 mice were randomly divided into normal control group(Control),model group(UC),MSLZ group and MSLZ+sh-Wnt1 group.Except for Control group,other groups were treated with sodium dextran sulfate(DSS)to establish UC model.Mice in Control,UC and MSLZ groups were intraperitoneally injected 5×109 pfu/ml NC-shRNA.Mice in MSLZ+sh-Wnt1 group were intraperi-toneally injected 5×109 pfu/ml shRNA-Wnt1.Mice in MSLZ group and MSLZ+sh-Wnt1 group were gavaged with 400 mg/kg MSLZ every day,and mice in Control and UC groups were gavaged with sterile distilled water of same dose every day.Colon length of mice in each group was detected.Kit was used to detect contents of D-lactate(D-LA),lipopolysaccharide(LPS)and activity of diamine oxidase(DAO)in serum of mice in each group.TUNEL staining was used to detect apoptosis in colon tissue of mice in each group.Immunohistochemistry was used to detect expressions of mucin 2(MUC2)and Occludin in colon tissues.Western blot was used to detect expressions of Wnt1,β-catenin,B cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Results:MSLZ could signi-ficantly increase length of colon,increase expressions of MUC2,Occludin,Wnt1,β-catenin and Bcl-2 in colon tissue,decrease levels of D-LA,LPS,DAO in serum,cell apoptosis rate and expression of Bax in colon tissue,while MSLZ+sh-Wnt1 could partially reverse protective effect of MSLZ on colon barrier function(all P<0.05).Conclusion:MSLZ can inhibit apoptosis of colon mucosa in UC mice,alleviate pathological damage of colon tissue,and ameliorate barrier function of colon mucosa,which may be related to activation of Wnt1 signaling pathway.
3.A family study of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy caused by a new locus of HTRA1 mutation
Xiaohong QIN ; Xuemei LIU ; Xianfeng QU ; Fumin WANG ; Jun XIAO ; Jieying LI
Chinese Journal of Neuromedicine 2024;23(4):397-400
Objective:To analyze the clinical and genetic characteristics of a family of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) caused by a new locus of HTRA1 mutation. Methods:The medical history and clinical data of a patient with CARASIL were collected, and genetic test was performed on some family members to observe the HTRA1 mutation. Results:The proband presented with cognitive impairment, suspicious lumbar lesions, and alopecia. Cranial imaging revealed extensive blank brain lesions and multiple microbleeding foci. The mother of the proband had psychiatric symptoms and stroke once, and the sixth younger sister had history of dementia and hypertension. Genetic test revealed that the proband and his two sons carried HTRA1 heterogenic mutation c.888C>G (p.I296M), and the two sons had alopecia. Conclusion:The c.888C>G(p.I296M) may be a new pathogenic mutation site of CARASIL.
4.Effect of dexmedetomidine combined with esketamine anesthesia in non-cardiac surgery for coronary artery disease
Dongsheng WANG ; Congli ZHANG ; Yang ZHANG ; Qin ZHUANG ; Xiaohong LI
Journal of Shenyang Medical College 2024;26(3):261-266
Objective:To analyze the effect of dexmedetomidine combined with esketamine anesthesia on non-cardiac surgery for coronary heart disease and the effect on hemodynamics,stress response and postoperative complications of patients.Method:A total of 106 patients with coronary heart disease who were going to undergo laparoscopic abdominal surgery from Oct 2021 to Nov 2022 in our hospital were selected and randomly divided into the control group and the observation group,with 53 cases in each group.All patients underwent conventional surgical treatment.The control group was given dexmedetomidine anesthesia,while the observation group was given dexmedetomidine combined with esketamine anesthesia.The surgical indicators,incidence of postoperative complications,diastolic blood pressure(DBP),systolic blood pressure(SBP),pain visual analog scale(VAS),Ramsay sedation score,and the levels of oxide dismutase(SOD),malondialdehyde(MDA),cortisol(Cor)and blood glucose(GLU)were compared between the two groups.Results:There was no statistically significant difference in the operation time between the two groups(P>0.05),but the postoperative sufentanil dosage of the observation group was lower than that of the control group,and the number of effective compressions was higher than that of the control group(P<0.05).At 12 h postoperatively,there was no significant difference between the VAS score and Ramsay sedation score of the two groups(P>0.05),and the VAS score and Ramsay sedation score in the observation group were better than those in the control group at 4 h and 8 h postoperatively(P<0.05).The levels of MDA,GLU and Cor in both groups increased and the level of SOD decreased at 4 h postoperatively(P<0.05),and the level of SOD in the observation group was higher than that of the control group,and the levels of MDA,GLU and Cor were lower than those of the control group(P<0.05).Before anesthesia,there was no statisti-cally significant difference in hemodynamic indexes between the two groups(P>0.05).Compared with before anesthesia,there were changes in HR,SBP,DBP,and RR of the two groups at the end of the operation and 24 h after the operation(P<0.05),and the HR,SBP,DBP,and RR of the observation group were better than those of the control group(P<0.05).The incidence of postoperative complications in the observation group was lower than that in the control group(P<0.05).Conclusion:Dexmedetomidine combined with esketamine anesthesia can effectively stabilize the hemodynamics of patients,reduce postoperative stress response,and reduce postoperative complications.
5.Experience of Integrative Palliative Care at Peking Union Medical College Hospital
Ruixuan GENG ; Ying ZHENG ; Chenchen SUN ; Xi ZENG ; Hongyan FANG ; Wenqian ZHAN ; Yuanfeng YU ; Qin YANG ; Xiaoyan DAI ; Xiaohong NING
Acta Academiae Medicinae Sinicae 2024;46(5):706-710
Objective To summarize the experience of integrative palliative care at Peking Union Medi-cal College Hospital and provide a reference for promoting the integrative palliative care model.Methods Twenty cases receiving integrative palliative care at Peking Union Medical College Hospital were collected.The clinical characteristics,reasons for initiating integrative palliative care,the process of integrative palliative care,and feedback from these cases were summarized.Results Insomnia(11 cases,55%)and pain(9 cases,45%)were the most common symptoms requiring control in the 20 cases.The integrative palliative care team assisted in medical decision-making for 17 cases(85%),prepared end-of-life for 9 cases(45%),assisted in the transfer for 3 cases(15%),and provided comfort care for all the 20 cases(100%).Conclusions The integrative palliative care model can help alleviate suffering in end-of-life patients and provide support to patients'families and the original medical teams.This model is worth further promotion within class A tertiary hospitals.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Chinese expert consensus on targeted and immunotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer
Ping JIANG ; Zi LIU ; Lichun WEI ; Yunyan ZHANG ; Fengju ZHAO ; Xiangkun YUAN ; Yipeng SONG ; Jing BAI ; Xiaofan LI ; Baosheng SUN ; Lijuan ZOU ; Sha LI ; Yuhua GAO ; Yanhong ZHUO ; Song GAO ; Qin XU ; Xiaohong ZHOU ; Hong ZHU ; Junjie WANG
Chinese Journal of Radiation Oncology 2024;33(10):893-901
Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.
8.Moderating effect of salidroside on intestinal microbiota in mice exposed to PM2.5
Siqi LI ; Chen LIU ; Weihong XU ; Wenbo WU ; Ruixi ZHOU ; Limin ZHANG ; Chao SONG ; Yumei LIU ; Fengjiao TAN ; Mengxiao LUAN ; Xiaolin HAN ; Jinfeng TAN ; Li YU ; Dongqun XU ; Qin WANG ; Xiaohong LI ; Wanwei LI
Journal of Environmental and Occupational Medicine 2024;41(2):125-132
Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.
9.The Association between Ophthalmic Artery Doppler Variables and the Severi-ty of Pre-eclampsia:a Meta-analysis
Li DAI ; Xiaohong WEI ; Lingyun LIAO ; Yangxue YIN ; Qin XU ; Shuangshuang XIE ; Rong ZHOU
Journal of Practical Obstetrics and Gynecology 2024;40(2):153-158
Objective:To investigate the association between the Doppler variables of the ophthalmic artery with the severity of preeclampsia(PE).Methods:Systematic literature was searched between January 1995 and March 2023 in PubMed,Web of Science,Embase,and the Cochrane Library.Studies comparing ophthalmic artery Doppler variables,including peak systolic velocity(PSV),end-diastolic velocity(EDV),resistive index(Rl),pulsa-tility index(PI),and peak ratio(PR,the ratio of the flow velocity of the second peak to that of the initial peak)in patients with PE,severe preeclampsia(sPE),and healthy pregnant women were included.The random-effects model was adopted as the method of pooled analysis,and the I2value was used to assess heterogeneity.The pooled standardized mean difference(SMD)with 95%confidence interval(CI)was used to estimate the associa-tion between ophthalmic artery Doppler variables and PE patient's characteristics.Results:Eight retrospective studies were eventually included in this Meta-analysis.Our pooled results suggested that compared with PE ca-ses,sPE patients had lower PI levels(SMD-0.56,95%CI-0.92~-0.20,P=0.000),higher EDV levels(SMD 0.47,95%CI 0.12~0.83,P=0.028)and higher PR levels(SMD0.96,95%CI 0.13~1.78,P=0.023).Howev-er,there was no significant difference between PE and sPE patients about the PSV and RI(P=0.361,P=0.626).Conclusions:This review demonstrates that ophthalmic artery Doppler variables(PI,EDV and PR)could be useful for predicting PE and PE development(especially in identifying sPE),which in turn may help the practitioner in the management of these complicated cases and in taking early necessary precautions.
10.Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway
Gang LIU ; Yaqi ZHANG ; Lingling QIN ; Chengfei ZHANG ; Qiue ZHANG ; Huizhong BAI ; Yi ZHAO ; Tonghua LIU ; Xiaohong MU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):75-82
ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 (AMPK/PGC-1α/SIRT3) signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling, they were randomly divided into high, medium, and low dose Tangbikang granule groups (2.5, 1.25, 0.625 g·kg-1·d-1) and lipoic acid group (0.026 8 g·kg-1·d-1), and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4, 8, 12 weeks after intervention. At the 12th week, motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), nerve blood flow velocity, mechanical pain threshold, and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin (HE) staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in sciatic nerve were determined by enzyme-related immunosorbent assay (ELISA). The mRNA expressions of AMPKα, AMPKβ, PGC-1α, and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction (Real-time PCR). ResultCompared with the normal group, fasting blood glucose in the model group was increased at each time point (P<0.01). The mechanical pain threshold was decreased (P<0.05), and the incubation time of the hot plate was extended (P<0.01). MNCV, SNCV, and nerve blood flow velocity decreased (P<0.05). The expression level of SOD was decreased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were increased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were decreased (P<0.01). The structure of sciatic nerve fibers in the model group was loose, and the arrangement was disordered. The demyelination change was obvious. Compared with the model group, the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks (P<0.01). The mechanical pain threshold increased (P<0.05). The incubation time of the hot plate was shortened (P<0.01). MNCV, SNCV, and Flux increased (P<0.05). The expression level of SOD was increased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were decreased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were increased (P<0.01). The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged, with only a few demyelinating changes. The high, medium, and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.

Result Analysis
Print
Save
E-mail