[1]司长峰,卜荔,徐楠,等.柴胡皂苷D对糖尿病视网膜病变大鼠的治疗作用[J].眼科新进展,2021,41(10):925-929.[doi:10.13389/j.cnki.rao.2021.0194]
 SI Changfeng,BU Li,XU Nan,et al.Therapeutical effect of Saikosaponin D on diabetic retinopathy of rats[J].Recent Advances in Ophthalmology,2021,41(10):925-929.[doi:10.13389/j.cnki.rao.2021.0194]
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柴胡皂苷D对糖尿病视网膜病变大鼠的治疗作用/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年10期
页码:
925-929
栏目:
实验研究
出版日期:
2021-10-05

文章信息/Info

Title:
Therapeutical effect of Saikosaponin D on diabetic retinopathy of rats
作者:
司长峰卜荔徐楠项燕顾永昊
239000 安徽省滁州市,滁州市第一人民医院眼科(司长峰,卜荔,徐楠,项燕);230031 安徽省合肥市,安徽省立医院眼科(顾永昊)
Author(s):
SI Changfeng1BU Li1XU Nan1XIANG Yan1GU Yonghao2
1.Department of Ophthalmology,the First People’s Hospital of Chuzhou,Chuzhou 239000,Anhui Province,China
2.Department of Ophthalmology,Anhui Provincial Hospital,Hefei 230031,Anhui Province,China
关键词:
柴胡皂苷D糖尿病视网膜病变微血管渗透性炎症
Keywords:
saikosaponin D diabetic retinopathy microvascular permeability inflammation
分类号:
R774
DOI:
10.13389/j.cnki.rao.2021.0194
文献标志码:
A
摘要:
目的 探究柴胡皂苷D(SSD)对糖尿病视网膜病变(DR)大鼠视网膜的保护作用及其机制。方法 40只SD大鼠随机分为正常对照(Con)组、DR组、低剂量SSD组和高剂量SSD组,每组各10只。DR组、低剂量SSD组和高剂量SSD组通过高脂高糖饮食联合腹腔注射链脲佐菌素(STZ)构建糖尿病大鼠模型,然后对糖尿病大鼠持续喂养高脂高糖饮食12周构建DR大鼠模型,其中低剂量SSD组、高剂量SSD组大鼠在持续高脂高糖喂养期间分别给予口服1 mg·kg-1·d-1和5 mg·kg-1·d-1 SSD。Con组大鼠全程采用标准饲料喂养,且不给予STZ注射。在喂养方案结束时,异硫氰酸荧光素-葡聚糖(FITC-Dextran)染色评估视网膜微血管的渗透性;过碘酸雪夫(PAS)染色观察视网膜微血管病变程度;ELISA检测视网膜组织中肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6和IL-1β的表达水平;Western blot检测视网膜组织中咬合蛋白(Occludin)、闭合蛋白5(Claudin-5)、闭锁小带蛋白1(ZO-1)、血管内皮生长因子α(VEGF-α)、胶质纤维酸性蛋白(GFAP)和血管内皮细胞黏附分子1(VCAM-1)的蛋白表达水平。结果 与Con组比较,DR组大鼠视网膜微血管的渗透性增加,视网膜毛细血管网中无细胞毛细血管(AC)和周细胞丢失(PL)的相对比例均增加,视网膜组织中TNF-α、IL-6、IL-1β、VEGF-α、GFAP和VCAM-1的表达水平均升高,而Occludin、Claudin-5和ZO-1的表达水平均降低(均为P<0.05)。与DR组比较,低剂量SSD组、高剂量SSD组大鼠视网膜微血管的渗透性均降低,视网膜毛细血管网中AC和PL的相对比例均降低,视网膜组织中TNF-α、IL-6、IL-1β、VEGF-α、GFAP和VCAM-1的表达水平均降低,而Occludin、Claudin-5和ZO-1表达水平均升高(均为P<0.05);其中,高剂量SSD组大鼠上述指标均较低剂量SSD组大鼠变化更明显(均为P<0.05)。结论 SSD可能通过减轻视网膜微血管渗透性和炎症反应而发挥对DR大鼠视网膜的治疗作用。
Abstract:
Objective To investigate the protective effect and mechanism of saikosaponin D (SSD) on the retina of diabetic retinopathy (DR) of rats.Methods Forty SD rats were randomly divided into normal control (Con) group, DR group, low-dose SSD group and high-dose SSD group, with 10 rats each. DR group, low-dose SSD group and high-dose SSD group were fed with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) to construct diabetes mellitus (DM) rat model. The DM rats were fed with high-fat and high-sugar diet continuously for 12 weeks to build DR rat model; the low- and high-dose SSD groups were orally given 1 mg·kg-1·d-1 and 5 mg·kg-1·d-1 SSD during continuous high-fat and high-sugar feeding period, respectively. Con group was fed with standard diet throughout the whole process without STZ injection. At the end of the feeding period, the permeability of retinal microvessels was evaluated by FITC-Dextran; the retinal microvascular lesions were observed by periodic acid-schiff (PAS) staining. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in the retina were detected by ELISA assay; the protein expression levels of Occludin, Claudin-5, zonula occludens protein-1 (ZO-1), vascular endothelial growth factor-α (VEGF-α), glial fibrillary acidic protein (GFAP) and vascular endothelial cell adhesion molecule-1 (VCAM-1) in the retina were detected by Western blot. Results Compared with Con group, the permeability of retinal microvessels, the relative proportions of acellular capillaries (AC) and pericyte loss (PL), and the levels of TNF-α, IL-6, IL-1β, VEGF-α, GFAP and VCAM-1 in retina in DR group were increased, while the expression levels of Occludin, Claudin-5 and ZO-1 were decreased (all P<0.05). Compared with DR group, the permeability of retinal microvessels, the relative proportions of AC and PL, and the levels of TNF-α, IL-6, IL-1β, VEGF-α, GFAP and VCAM-1 in retina in low- and high-dose groups were decreased, while the expression levels of Occludin, Claudin-5 and ZO-1 were increased (all P<0.05). Among them, the changes in the above indicators in the high-dose SSD group were more significant than those in the low-dose SSD group (all P<0.05).Conclusion SSD may play a protective role on the retina of DR rats by reducing the permeability and inflammation of retinal microvessels.

参考文献/References:

[1] FLAXMAN S R,BOURNE R R A,RESNIKOFF S,ACKLAND P,BRAITHWAITE T,CICINELLI M V,et al.Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis[J].Lancet Glob Health,2017,5(12):e1221-e1234.
[2] 李卫斌,胡宝平,项炫萌.HPLC法测定不同产地柴胡中柴胡皂苷A、C、D的含量[J].甘肃医药,2019,38(1):66-67,86.
LI W B,HU B P,XIANG X M.The content of saikosaponin A,C and D in bupleurum from different areas determined by HPLC[J].Gansu Med J,2019,38(1):66-67,86.
[3] WONG V K,ZHANG M M,ZHOU H,LAM K Y,CHAN P L,LAW C K,et al.Saikosaponin-D enhances the anticancer potency of TNF-α via overcoming its undesirable response of activating NF-Kappa B signalling in cancer cells[J].Evid Based Complement Alternat Med,2013,2013:745295.
[4] 王宝峰,程延安,党双锁, 刘振国,贾晓黎,马红兵,等.柴胡皂甙-D对鸡胚血管形成抑制作用的研究[J].中国中西医结合杂志,2009,29(5): 425-429.
WANG B F,CHENG Y A,DANG S S,LIU Z G,JIA X L,MA H B,et al.Angiogenesis inhibitory effect of saikosaponin-D on chicken embryo[J].Chin J Integr Trad West Med,2009,29(5):425-429.
[5] AL-KHARASHI A S.Role of oxidative stress,inflammation,hypoxia and angiogenesis in the development of diabetic retinopathy[J].Saudi J Ophthalmol,2018,32(4):318-323.
[6] LEI X W,LI Q,ZHANG J Z,ZHANG Y M,LIU Y,YANG K H.The protective roles of folic acid in preventing diabetic retinopathy are potentially associated with suppressions on angiogenesis,inflammation,and oxidative stress[J].Ophthalmic Res,2019,62(2):80-92.
[7] AL-AWAR A,KUPAI K,VESZELKA M,SZCS G,ATTIEH Z,MURLASITS Z,et al.Experimental diabetes mellitus in different animal models[J].J Diabetes Res,2016,2016:9051426.
[8] 李琳,李彦林,周云丰,王丽丽,李志强,葛争艳,等.长时间甲醛固定的大鼠视网膜组织胰蛋白酶消化方法探讨[J].中国药理学通报,2014,30(12):1704-1708.
LI L,LI Y L,ZHOU Y F,WANG L L,LI Z Q,GE Z Y,et al.Trypsin digestion method for the long-term formalin-fixed retinal in rats[J].Chin Pharmacol Bull,2014,30(12):1704-1708.
[9] NCD Risk Factor Collaboration (NCD-RISC).Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants[J].Lancet,2016,387(10027):1513-1530.
[10] YAU J W,ROGERS S L,KAWASAKI R,LAMOUREUX E L,KOWALSKI J W,BEK T,et al.Global prevalence and major risk factors of diabetic retinopathy[J].Diabetes Care,2012,35(3):556-564.
[11] HARDING J L,PAVKOV M E,MAGLIANO D J,SHAW J E,GREGG E W.Global trends in diabetes complications:a review of current evidence[J].Diabetologia,2019,62(1):3-16.
[12] UEMURA A.Pharmacologic management of diabetic retinopathy[J].J Biochem,2018,163(1):3-9.
[13] STITT A W,CURTIS T M,CHEN M,MEDINA R J,MCKAY G J,JENKINS A,et al.The progress in understanding and treatment of diabetic retinopathy[J].Prog Retin Eye Res,2016,51:156-186.
[14] PANG B,LI Q W,QIN Y L,DONG G T,FENG S,WANG J,et al.Traditional Chinese medicine for diabetic retinopathy:a systematic review and meta-analysis[J].Medicine (Baltimore),2020,99(7):e19102.
[15] SHEN C Y,JIANG J G,YANG L,WANG D W,ZHU W.Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery[J].Br J Pharmacol,2017,174(11):1395-1425.
[16] KLAASSEN I,VAN NOORDEN C J,SCHLINGEMANN R O.Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions[J].Prog Retin Eye Res,2013,34:19-48.
[17] KADY N M,LIU X,LYDIC T A,SYED M H,NAVITSKAYA S,WANG Q,et al.ELOVL4-mediated production of very long-chain ceramides stabilizes tight junctions and prevents diabetes-induced retinal vascular permeability[J].Diabetes,2018,67(4):769-781.
[18] SEMERARO F,MORESCALCHI F,CANCARINI A,RUSSO A,REZZOLA S,COSTAGLIOLA C.Diabetic retinopathy,a vascular and inflammatory disease:therapeutic implications[J].Diabetes Metab,2019,45(6):517-527.
[19] RBSAM A,PARIKH S,FORT P E.Role of inflammation in diabetic retinopathy[J].Int J Mol Sci,2018,19(4):942.
[20] MA M,ZHAO S,ZHANG J,SUN T,FAN Y,ZHENG Z.High glucose-induced TRPC6 channel activation decreases glutamate uptake in rat retinal Muller cells[J].Front Pharmacol,2020,10:1668.
[21] COUGHLIN B A,FEENSTRA D J,MOHR S.Müller cells and diabetic retinopathy[J].Vision Res,2017,139: 93-100.
[22] WANG J,XU X,ELLIOTT M H,ZHU M,LE Y Z.Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage[J].Diabetes,2010,59(9): 2297-305.
[23] DAZ-CORNGUEZ M,LIN C M,LIEBNER S,ANTONETTI D A.Norrin restores blood-retinal barrier properties after vascular endothelial growth factor-induced permeability[J].J Biol Chem,2020,295(14):4647-4660.
[24] KHALFAOUI T,LIZARD G,BELTAIEF O,COLIN D,BEN HAMIDA J,ERRAIS K,et al.Immunohistochemical analysis of cellular adhesion molecules (ICAM-1,VCAM-1) and VEGF in fibrovascular membranes of patients with proliferative diabetic retinopathy: preliminary study[J].Pathol Biol (Paris),2009,57(7-8):513-517.
[25] OUYANG H,MEI X,ZHANG T,LU B,JI L.Ursodeoxycholic acid ameliorates diabetic retinopathy via reducing retinal inflammation and reversing the breakdown of blood-retinal barrier[J].Eur J Pharmacol,2018,840:20-27.
[26] CUI B,SUN J H,XIANG F F,LIU L,LI W J.Aquaporin 4 knockdown exacerbates streptozotocin-induced diabetic retinopathy through aggravating inflammatory response[J].Exp Eye Res,2012,98:37-43.

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备注/Memo

备注/Memo:
安徽省自然科学基金项目(编号:1908085MH254)
更新日期/Last Update: 2021-10-05