Z Y Wang, S Q Yang, S X Wang, X Chen, M Z Cheng, Y F Yu
{"title":"[二硒烯交联纳米虾青素对庆大霉素致小鼠前庭毒性的保护作用及其机制]。","authors":"Z Y Wang, S Q Yang, S X Wang, X Chen, M Z Cheng, Y F Yu","doi":"10.3760/cma.j.cn112137-20250118-00159","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objective:</b> To investigate the protective effect and its mechanism of intratympanic administration of diselenide cross-linked nano-carriers of astaxanthin (AST@dSe-AFT) on vestibular toxicity induced by gentamicin (GM) in mice. <b>Methods:</b> Forty-two male ICR mice aged 6-8 weeks were randomly divided into seven groups according to a random number table: control group, GM injury group, natural astaxanthin (AST) protection group (GM+AST group), and four AST@dse-AFT protection groups (GM+AST/NP 0.1 group, GM+AST/NP 1 group, GM+AST/NP 10 group, and GM+AST/NP 100 group), which were given 0.1, 1, 10, and 100 mg/ml AST@dSe-AFT, respectively. The control group did not receive any intervention;the GM injury group was established by intraperitoneal injection of 200 mg/kg GM for 7 consecutive days to construct a vestibular injury model; the GM+AST group received an intratympanic injection of 0.1 ml of 1 mg/ml AST dimethyl sulfoxide solution, while the remaining four groups received intratympanic injections of corresponding concentrations of AST@dSe-AFT. Afterwards, a vestibular injury model was constructed. The vestibular function was evaluated through swimming experiments, balance beam experiments, and rotating rod fatigue instrument experiments. The morphology and number of hair cells in the macula of the utricle and saccule were observed by immunofluorescence staining, and the expression levels of apoptosis-related proteins in the vestibular tissues were analyzed. <b>Results:</b> The behavioral experiments revealed that the balance beam passing time in the GM+AST/NP 10 and GM+AST/NP 100 groups were shorter than that in the GM injury group [(18.8±1.5) and (19.3±1.2) vs (33.9±2.0) s, all <i>P</i><0.05], and the total distance,dwell time and speed of the rotating rod fatigue test were higher than those in the GM injury group [(2.9±0.4), (3.3±0.6), (1.0±0.1) m; (121.6±9.2), (125.7±11.4), (70.9±5.1) s; (30.7±2.4), (31.7±3.0), (17.2±1.4) m/s, respectively, all <i>P</i><0.05]. Immunofluorescence staining results showed that the number of hair cells in the utricle macula in the GM+AST/NP 10 and GM+AST/NP 100 groups were higher than that in the GM injury group (all <i>P</i><0.05). The expression of apoptosis-related proteins Cleaved caspase 3, Cleaved caspase 9, and Cleaved PARP-1 in the GM+AST/NP 10 group was lower than that in the GM injury group (all <i>P</i><0.05). <b>Conclusions:</b> Intratympanic injection of AST@dSe-AFT can antagonize GM-induced vestibular damage, and its protective effect on vestibular function may be related to the inhibition of hair cell apoptosis.</p>","PeriodicalId":24023,"journal":{"name":"Zhonghua yi xue za zhi","volume":"105 26","pages":"2218-2226"},"PeriodicalIF":0.0000,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Protective effect and its mechanism of diselenide cross-linked nano-loaded astaxanthin on gentamicin-induced vestibular toxicity in mice].\",\"authors\":\"Z Y Wang, S Q Yang, S X Wang, X Chen, M Z Cheng, Y F Yu\",\"doi\":\"10.3760/cma.j.cn112137-20250118-00159\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Objective:</b> To investigate the protective effect and its mechanism of intratympanic administration of diselenide cross-linked nano-carriers of astaxanthin (AST@dSe-AFT) on vestibular toxicity induced by gentamicin (GM) in mice. <b>Methods:</b> Forty-two male ICR mice aged 6-8 weeks were randomly divided into seven groups according to a random number table: control group, GM injury group, natural astaxanthin (AST) protection group (GM+AST group), and four AST@dse-AFT protection groups (GM+AST/NP 0.1 group, GM+AST/NP 1 group, GM+AST/NP 10 group, and GM+AST/NP 100 group), which were given 0.1, 1, 10, and 100 mg/ml AST@dSe-AFT, respectively. The control group did not receive any intervention;the GM injury group was established by intraperitoneal injection of 200 mg/kg GM for 7 consecutive days to construct a vestibular injury model; the GM+AST group received an intratympanic injection of 0.1 ml of 1 mg/ml AST dimethyl sulfoxide solution, while the remaining four groups received intratympanic injections of corresponding concentrations of AST@dSe-AFT. Afterwards, a vestibular injury model was constructed. The vestibular function was evaluated through swimming experiments, balance beam experiments, and rotating rod fatigue instrument experiments. The morphology and number of hair cells in the macula of the utricle and saccule were observed by immunofluorescence staining, and the expression levels of apoptosis-related proteins in the vestibular tissues were analyzed. <b>Results:</b> The behavioral experiments revealed that the balance beam passing time in the GM+AST/NP 10 and GM+AST/NP 100 groups were shorter than that in the GM injury group [(18.8±1.5) and (19.3±1.2) vs (33.9±2.0) s, all <i>P</i><0.05], and the total distance,dwell time and speed of the rotating rod fatigue test were higher than those in the GM injury group [(2.9±0.4), (3.3±0.6), (1.0±0.1) m; (121.6±9.2), (125.7±11.4), (70.9±5.1) s; (30.7±2.4), (31.7±3.0), (17.2±1.4) m/s, respectively, all <i>P</i><0.05]. Immunofluorescence staining results showed that the number of hair cells in the utricle macula in the GM+AST/NP 10 and GM+AST/NP 100 groups were higher than that in the GM injury group (all <i>P</i><0.05). The expression of apoptosis-related proteins Cleaved caspase 3, Cleaved caspase 9, and Cleaved PARP-1 in the GM+AST/NP 10 group was lower than that in the GM injury group (all <i>P</i><0.05). <b>Conclusions:</b> Intratympanic injection of AST@dSe-AFT can antagonize GM-induced vestibular damage, and its protective effect on vestibular function may be related to the inhibition of hair cell apoptosis.</p>\",\"PeriodicalId\":24023,\"journal\":{\"name\":\"Zhonghua yi xue za zhi\",\"volume\":\"105 26\",\"pages\":\"2218-2226\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-07-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Zhonghua yi xue za zhi\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3760/cma.j.cn112137-20250118-00159\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zhonghua yi xue za zhi","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3760/cma.j.cn112137-20250118-00159","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
[Protective effect and its mechanism of diselenide cross-linked nano-loaded astaxanthin on gentamicin-induced vestibular toxicity in mice].
Objective: To investigate the protective effect and its mechanism of intratympanic administration of diselenide cross-linked nano-carriers of astaxanthin (AST@dSe-AFT) on vestibular toxicity induced by gentamicin (GM) in mice. Methods: Forty-two male ICR mice aged 6-8 weeks were randomly divided into seven groups according to a random number table: control group, GM injury group, natural astaxanthin (AST) protection group (GM+AST group), and four AST@dse-AFT protection groups (GM+AST/NP 0.1 group, GM+AST/NP 1 group, GM+AST/NP 10 group, and GM+AST/NP 100 group), which were given 0.1, 1, 10, and 100 mg/ml AST@dSe-AFT, respectively. The control group did not receive any intervention;the GM injury group was established by intraperitoneal injection of 200 mg/kg GM for 7 consecutive days to construct a vestibular injury model; the GM+AST group received an intratympanic injection of 0.1 ml of 1 mg/ml AST dimethyl sulfoxide solution, while the remaining four groups received intratympanic injections of corresponding concentrations of AST@dSe-AFT. Afterwards, a vestibular injury model was constructed. The vestibular function was evaluated through swimming experiments, balance beam experiments, and rotating rod fatigue instrument experiments. The morphology and number of hair cells in the macula of the utricle and saccule were observed by immunofluorescence staining, and the expression levels of apoptosis-related proteins in the vestibular tissues were analyzed. Results: The behavioral experiments revealed that the balance beam passing time in the GM+AST/NP 10 and GM+AST/NP 100 groups were shorter than that in the GM injury group [(18.8±1.5) and (19.3±1.2) vs (33.9±2.0) s, all P<0.05], and the total distance,dwell time and speed of the rotating rod fatigue test were higher than those in the GM injury group [(2.9±0.4), (3.3±0.6), (1.0±0.1) m; (121.6±9.2), (125.7±11.4), (70.9±5.1) s; (30.7±2.4), (31.7±3.0), (17.2±1.4) m/s, respectively, all P<0.05]. Immunofluorescence staining results showed that the number of hair cells in the utricle macula in the GM+AST/NP 10 and GM+AST/NP 100 groups were higher than that in the GM injury group (all P<0.05). The expression of apoptosis-related proteins Cleaved caspase 3, Cleaved caspase 9, and Cleaved PARP-1 in the GM+AST/NP 10 group was lower than that in the GM injury group (all P<0.05). Conclusions: Intratympanic injection of AST@dSe-AFT can antagonize GM-induced vestibular damage, and its protective effect on vestibular function may be related to the inhibition of hair cell apoptosis.