目的 探讨明目驻景丸对大鼠视神经损伤后视网膜神经节细胞(RGCs)的抗凋亡作用,以及对视网膜相关基因表达的影响.方法 将健康SD大鼠随机均分为正常组、模型组和明目驻景丸组,除正常组外,其余两组均使用微型视神经夹造成大鼠右眼视神经损伤模型.正常组和模型组常规饲养,每日定时定量给予蒸馏水灌胃,明目驻景丸组每日定时定量给予明目驻景丸灌胃.造模7d后,采用TUNEL法检测各组大鼠RGCs的凋亡情况;造模10 d后,采用RT-PCR和Western blot法检测大鼠视网膜组织中Bax、Bcl-2基因及蛋白的表达情况.结果 造模7d后,明目驻景丸组大鼠RGCs的凋亡数量显著低于模型组;与模型组比较,造模10 d后,明目驻景丸组Bax基因和蛋白的表达量显著降低,Bcl-2基因和蛋白的表达量显著升高.结论 明目驻景丸可能是通过减少大鼠视神经钳夹损伤后RGCs的凋亡,降低视网膜组织中Bax基因和蛋白的表达,同时促进Bcl-2基因和蛋白的表达,从而发挥其对视神经损伤的保护作用.

Currently, adipocytes and macrophages are considered to be key cell types of breast cancer (BC) tissues. With the emergence of crown-like structures (CLS), cancer-associated adipocytes (CAAs) and tumour-associated macrophages (TAMs) are formed respectively in tumor microenvironment (TME). Both of them affect the progress of breast cancer, while forming crosstalk in the tumour tissue. CAAs play an important role, which produces hypoxia and inflammation environment and aggravates this environment. The formation and secretion of TAMs with M2 phenotypic characteristics, such as HIF-1α, and TNF-α, affect the progress of cancer cells by interfering with the secretion of MCP-1 by CAAs. Therefore, the interaction between CAAs and TAMs may be an effective therapeutic target for breast cancer. In this review, we focus on the biological effects of two types of cells in breast cancer, in order to better explain the crosstalk between them and provide new ideas for the future treatment of breast cancer.

目的 观察通络驻景丸对糖尿病大鼠血-视网膜屏障的保护作用的影响,并探讨其可能的作用机制.方法 取SD大鼠75只,随机分为5组:空白对照组,模型组,通络驻景丸低(TLP-L)、中(TLP-M)、高剂量(TLP-H)组,各15只.用链脲佐菌素(STZ)诱导制造SD大鼠糖尿病模型,模型成功1周后,除空白组、模型组灌胃给予等容积的蒸馏水,其他治疗组给予不同剂量通络驻景丸(TLP)药物治疗(分别是1.65、3.33、6.66 g生药/Kg).末次给药结束后,Western blot法测定视网膜白蛋白(Albumin)渗漏、视网膜组织中紧密连接蛋白中咬合蛋白(Occludin)、带状闭合蛋白ZO-1的蛋白表达水平;实时聚合酶链反应(RT-PCR)检测大鼠视网膜组织中Occludin mRNA的表达情况.结果 (1)Albumin渗漏:与模型组比较,通络驻景丸组大鼠视网膜组织中Albumin渗漏水平降低(tTLP-H=21.596,tTLP-M=10.210,tTLP-L=6.861,均P=0.000);(2)Occludin蛋白及mRNA:与模型组比较,通络驻景丸给药组大鼠视网膜组织Occludin的蛋白表达水平升高(tTLP-H=14.216,tTLP-M=6.679,均P=0.000),Occludin mRNA表达水平均有不同程度的升高(tTLP-H=4.845,PTLP-H=0.001;tTLP-M=3.835,PTLP-M=0.003),均有统计学意义(P<0.05);(3)ZO-1蛋白:与模型组比较,通络驻景丸给药组大鼠视网膜组织ZO-1的蛋白表达水平升高(tTLP-H=11.498,tTLP-M=5.694,均P=0.000).结论 通络驻景丸能降低糖尿病大鼠视网膜中Albumin渗漏,升高视网膜组织中紧密连接蛋白Occludin、ZO-1的蛋白表达和Occludin mRNA的表达情况,保护血-视网膜屏障.

糖尿病黄斑水肿是糖尿病视网膜病变患者视力下降的主要原因之一.中医药理论认为,糖尿病黄斑水肿多责于肝肾阴虚、脾虚湿盛、痰瘀互结,治当滋补肝肾、健脾利湿、化痰祛瘀.雷晓琴教授认为痰瘀互结贯穿于糖尿病黄斑水肿始终,故临床多从痰瘀论治,取得了较好疗效.

以中医虚、瘀(郁)病机为切入点,探索视神经萎缩的中医药治疗理论基础,分别从视神经萎缩的中医文献支撑、虚证、瘀血、从虚瘀(郁)论治视神经萎缩等几个方面阐述,旨在为临床与科研提供精准、切实的理论依据.

糖尿病黄斑水肿可造成中心视力的丧失,是引起糖尿病患者视力下降的主要原因之一,为耱尿病患者眼部常见的并发症.导师雷晓琴主任医师从水血互因论的角度出发,认为糖尿病黄斑水肿的主要病机为肝肾阴虚,气滞血瘀,瘀水互结,治疗当遵补益肝肾、行气活血、祛湿利水之法,随证化裁,临床疗效显著.

视神经萎缩属中医学“青盲”范畴,是导致视力不可逆性损伤的退行性病变,是临床致盲的重要原因之一.青盲的发生发展无外乎以下五方面因素:热病邪毒殃及正气;头眼外伤损及瞳神;情志不节气滞化火;肿瘤压迫血络不通;先天不足,精血失养.其病机归纳起来,统属“瘀、郁、虚”三个方面,主要病机关键系瘀血阻络为主,兼杂气血亏虚;因而治疗当遵化瘀通络,补益气血之法,随证化裁;临床遵此法,常能取得显著疗效.

目的:观察雷珠单抗玻璃体腔(PRN)注射治疗视网膜分支静脉阻塞继发黄斑水肿(BRVO-ME)的疗效.方法:纳入经临床检查确诊的BRVO-ME患者80例(80眼).所有患者均在雷珠单抗玻璃体腔首次注射后行玻璃体腔按需注射(1+PRN)治疗,随访6个月,每个月随访1次,观察最佳矫正视力(BCVA)及光学相干断层扫描(OCT)所测量的黄斑中心凹视网膜厚度(CM T)变化情况及两组注射次数的差异.结果:① 治疗前及治疗后6个月患者BCVA分别为(0.85±0.50)logMAR及(0.42±0.35)logMAR,两者相比差异有统计学意义(P<0.05);缺血型BRVO治疗前及治疗后6个月BCVA分别为(0.99±0.47)logMAR及(0.43±0.41)logMAR,两者相比差异有统计学意义(P<0.05),非缺血型BRVO治疗前及治疗后6个月BCVA分别为(0.81±0.53)logMAR及(0.41±0.32)logMAR,两者相比差异有统计学意义(P<0.05),两组患者间BCVA变化比较差异无统计学意义(P>0.05).②治疗前及治疗后6个月患者CMT分别为(625.62±172.40)μm和(260.27±101.81)μm,两者比较差异有统计学意义(P<0.01);缺血型BRV O治疗前及治疗后6个月CM T分别为(632.09±143.72)μm和(262.17±104.54)μm;非缺血型BRV O治疗前及治疗后6个月CM T分别为(621.42±190.10)μm和(257.43±121.47)μm;与治疗前相比,两组患者治疗后各个时间点CMT均有显著性下降,差异有统计学意义(P<0.05).治疗后各个时间点,两组间CM T比较差异无统计学意义(P>0.05).③6个月内患者的平均注射次数为(2.6±1.4)次,非缺血型BRVO平均注射次数为(2.3±1.2)次,缺血型BRVO患者的平均注射次数为(3.2±1.7)次,两组患者注射次数比较差异无统计学意义(P>0.05).结论:雷珠单抗玻璃体腔按需注射(1+PRN)对缺血型及非缺血型BRV O-M E患者效果显著,可有效改善视力,减轻黄斑水肿症状,并具有很好的安全性.

目的 观察通络驻景丸对糖尿病大鼠视网膜血管内皮生长因子(VEGF)表达水平的影响,并探讨其可能的作用机制.方法 链脲佐菌素(STZ)诱导SD大鼠糖尿病模型,并随机将造模成功的大鼠分为4组:模型组,通络驻景丸低、中、高剂量组.模型成功1周后,除空白组、模型组灌胃给予等容积的蒸馏水,其他治疗组给予不同剂量通络驻景丸药物治疗(分别是1.65、3.33、6.66 g生药/kg).给药12周后,ELISA试剂盒测定血清中VEGF的含量;实时聚合酶链反应(RT-PCR)检测大鼠视网膜组织中VEGF mRNA的表达情况;免疫组织化学法检测视网膜中VEGF蛋白表达情况.结果 与模型组比较,通络驻景丸给药组大鼠血清VEGF和视网膜VEGF mRNA表达水平均有不同程度的降低,其中通络驻景丸高剂量组降幅最大.免疫组化结果显示给予通络驻景丸后,视网膜中VEGF表达水平也降低.结论 通络驻景丸能降低糖尿病大鼠血清和视网膜中VEGF的表达水平,延缓DR病程的发展.

目的 研究基质金属蛋白酶抑制剂盐酸多西环素对兔角膜新生血管(corneal neovascularization,CNV)生长的影响.方法 成年大耳白兔33只(66眼),随机分为对照组、碱烧伤组和多西环素组.对照组3只(6眼)不做处理.剩余30只(60眼)利用1 mol·L-1 NaOH滤纸片建立双眼碱烧伤模型,右眼为多西环素组,左眼为碱烧伤组.碱烧伤组不给予药物治疗,多西环素组隔日结膜下注射0.1 mL注射用盐酸多西环素(10 g· L-1).观察兔CNV的生长情况,应用免疫组织化学化法检测角膜组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)、组织型金属蛋白酶抑制剂-2(tissue inhibitors of metalloproteinase-2,TIMP-2)的表达情况.结果 造模后3d,可见碱烧伤组和多西环素组CNV长入透明角膜.造模后4d、7d、14 d、21 d,多西环素组CNV的面积分别为(6.15±2.85) mm2、(14.39±4.04) mm2、(18.07±5.74) mm2、(19.44 ±6.95) mm2,碱烧伤组CNV的面积分别为(17.00±4.60) mm2、(37.93±6.91)mm2、(42.25±9.32) mm2、(38.81±4.87)mm2,各时间点多西环素组CNV的面积均明显小于碱烧伤组(均为P＜0.05).造模后1d、4d、7d、14 d、21 d,多西环素组角膜上皮层VEGF灰度值分别为167.74±10.59、140.14±12.14、128.69±9.21、103.06±8.29、176.16±9.72,碱烧伤组角膜上皮层VEGF灰度值分别为129.79±10.97、100.51±21.73、81.38±9.98、62.54±10.30、148.81±8.65,造模后各个时间点多西环素组VEGF的表达均明显少于碱烧伤组(均为P＜0.05).造模后4d、7d、14 d,多西环素组角膜上皮层MMP-2灰度值分别为83.50±14.81、123.42±16.20、110.90±8.98,碱烧伤组角膜上皮层MMP-2灰度值分别为65.27±12.84、91.31±13.22、94.28±6.46,造模后4d、7d、14 d多西环素组角膜上皮层MMP-2表达均明显低于碱烧伤组(均为P＜0.05).造模后21 d,角膜上皮层TIMP-2的表达最强,但造模后多西环素组角膜上皮层TIMP-2表达和碱烧伤组表达强度相似,两组比较差异无统计学意义(P＞0.05).结论 VEGF、MMP-2、TIMP-2在CNV发生发展中发挥着重要的调控作用,盐酸多西环素可通过抑制基质胶原纤维的降解来降低炎症反应,并通过抑制角膜碱烧伤后兔角膜组织中VEGF、MMP-2的表达,进而抑制CNV的发生发展.

目的:探讨通络驻景丸对糖尿病(DM)大鼠视网膜血流动力学、血液流变学与视网膜微血管周细胞、内皮细胞的影响.方法:取SPF级SD大鼠,随机取15只作为空白对照组,造模大鼠以剂量为60 mg/kg体质量腹腔注射链脲佐菌素(STZ),将造模成功(72 h后血糖≥16.7 mmol/L)的大鼠随机分为模型对照组、阳性药(羟苯磺酸钙150 mg/kg)对照组、通络驻景丸大(3.30 g/kg)、中(1.65 g/kg)、小(0.83 g/kg)剂量组.每日灌胃给药1次,连续24周.检测每组大鼠视网膜中央动静脉血流动力学、全血黏度、血浆黏度、血沉和视网膜毛细血管周细胞数目和内皮细胞数目.结果:与空白组比较,模型组大鼠视网膜中央动静脉血流速度,全血黏度、血浆黏度、血沉和视网膜周细胞的丢失、内皮细胞的增生,差异具有统计学意义(P＜0.05);与模型组比较,通络驻景丸各剂量组的上述指标变化,差异均具有统计学意义(P＜0.05).结论:通络驻景丸能明显改善糖尿病大鼠视网膜血流动力学和血液流变学,能显著减少视网膜微血管周细胞的丢失、抑制毛细血管内皮细胞的增生.

目的 观察通络驻景丸联合抗VEGF药物和激光光凝治疗糖尿病性黄斑水肿(DME)的临床疗效.方法 将104例(137只眼)DME患者随机分成治疗组(52例,68只眼)和对照组(52例,69只眼),治疗3个月,治疗结束后继续随访6个月,治疗组:通络驻景丸联合激光和抗VEGF药物治疗,对照组:安慰剂联合激光和抗VEGF药物治疗.比较两组患者治疗前及治疗3个月,治疗结束后随访3、6个月的最佳矫正视力(BCVA)、黄斑中心视网膜厚度(CRT)、黄斑区发生荧光渗漏情况,随访结束时黄斑水肿复发率和两组患眼平均所需注射抗VEGF药物次数.结果 治疗后3个月、治疗结束后随访3、6个月的BCVA、CRT、黄斑区发生荧光渗漏情况和治疗前比较均有统计学意义(P＜0.05),两组之间比较均无统计学意义(P＞0.05);治疗结束后随访6个月时黄斑水肿的复发率35.3％较对照组47.8％低(P＜0.05),治疗组患眼所需注射抗VEGF药物次数平均为3.9次,对照组为4.5次;两组患者治疗期间均未出现明显的药物不良反应.结论 通络驻景丸联合抗VEGF药物和激光光凝治疗DME能够有效提高患者视力、减轻黄斑水肿,防止水肿复发,减少玻璃体腔注药次数,降低费用及风险和并发症,值得临床推广应用.

通络驻景丸源于中医经典古方驻景丸,基于我们对驻景丸、加减驻景丸、驻景丸加减方的深入研究、临床应用和动物实验的不断探索总结的基础上,创制而成.临证加减化裁,治疗糖尿病性视网膜病变、年龄相关性黄斑变性、中心性浆液性脉络膜视网膜病变、视网膜静脉阻塞、高度近视黄斑病变等多种眼底病变,疗效确切.

OBJECTIVE To investigate the protective effects of Tongluo Zhujing pill on retina of rats with diabetes mellitus and its underlying mechanism. METHODS The diabetic model was established by intraperitoneal injection of streptozotocin (STZ). The model rats were randomly divided into model control group (DM group) and Tongluo Zhujing group (TLZJ group) with 20 rats in each group. Another 20 rats were assigned into normal control (NC) group. Rats in NC group and DM group were given distilled water by gavage, animals in TLZJ group were given Tongluo Zhujing decoction intragastrically. Six weeks and 12 weeks afterwards, immunohisto-chemical method and real-time quan-titative PCR were used respectively to detect the relative expression levels of Nrf2, HO-1 and VEGF in retinas of the rats. RESULTS The expressions of Nrf2, HO-1 and VEGF in different group were in consistency. Six weeks and twelve weeks after intervention , the expressions of each factor in DM group were higher than those in the NC group.The Nrf2 and HO-1 in TLZJ group were higher than those in the DM group,but the VEGF was lower than its counterparts (P＜0.05).After 12 weeks,the expressions of VEGF and Nrf2 in DM group were more than those indexes detected 6 weeks after treatment,but the HO-1 was lower; the Nrf2 and HO-1 in TLZJ group were higher than counter-parts at the prior time point, and the VEGF was lower (all P＜0.05).CONCLUSIONS Tongluo Zhujing pill effectively relieved oxidative stress injury and inhibited retinal proliferation in retina of DM rats, which might be related to the activation of Nrf2/ARE pathway and the expression of Nrf2, HO-1 and VEGF.

Objective: In this study, we investigate the protective effects of the Chinese herbal medicine prescription Zhujing pill (ZJP) on the development of diabetic retinopathy (DR) and explore the potential mechanisms. Materials and methods: Zhujing pill extract (ZJPE) was prepared, and the main components were identified by high-performance liquid chromatography (HPLC). Several serum and tissue (retina) parameters were measured, such as levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), advanced glycation end products (AGEs), and high sensitivity C-reactive protein (hsCRP). Aldose reductase (AR) activity and blood-retinal barrier (BRB) breakdown were determined. Finally, retinal electrophysiology and morphological changes were assayed. Results: In STZ-induced DM rats, ZJPE treatment restored the body weight decrease. DM rats showed decreased levels of SOD and GSH-Px and increased levels of IL-6, TNF-alpha, hsCRP, and MDA, whereas all these changes were significantly reversed by ZJPE administration. ZJPE alleviated BRB breakdown. Furthermore, ZJPE also alleviated the retinal electrophysiology changes and impaired morphology of the retina and lowered the high levels of TNF-alpha, IL-1 beta, ICAM-1, VEGF, AGEs, and AR in the retina. Conclusions: ZJPE treatment attenuated the progression of DR in STZ-induced diabetic rats.

目的:探讨通络驻景丸对糖尿病大鼠视网膜中HIF-1α及PDGF-B表达的影响.方法:除空白组外,SD大鼠腹腔注射链脲佐菌素建立糖尿病模型,造模成功的大鼠随机分为:模型组,通络驻景丸低、中、高剂量组.模型组和空白组给予蒸馏水作对照,通络驻景丸低、中、高剂量组给予不同剂量通络驻景丸药液治疗(分别是1.65、3.33、6.66g生药/kg).末次给药结束后,取大鼠全血测糖化血红蛋白水平;取大鼠视网膜,用RT-PCR检测各组大鼠视网膜中HIF-1αmRNA及PDGF-B mRNA的表达;ELIAS检测HIF-1α及PDGF-B蛋白表达.结果:模型组大鼠视网膜HIF-1αmRNA、PDGF-B mRNA水平比空白组显著升高,通络驻景丸给药组HIF-1 αmRNA、PDGF-B mRNA表达水平比模型组均有降低,且通络驻景丸高剂量组降幅最大.模型组大鼠HIF-1α、PDGF-B蛋白水平比空白组显著升高,通络驻景丸给药组HIF-1α、PDGF-B表达水平比模型组均有降低,且通络驻景丸高剂量组降幅最大.结论:研究显示通络驻景丸可能通过降低HIF-1α及PDGF-B表达,在糖尿病大鼠视网膜疾病的发生发展过程中起一定作用.

Ethnopharmacological relevance: According to ancient traditional Chinese medicine, Typhae Pollen (TP) is commonly used to treat fundus haemorrhage because it improves blood circulation. Aims of the study: This study evaluated the role of the main TP component, polysaccharides (TPP), on diabetic retinopathy (DR) and its possible mechanisms of inhibiting inflammation and improving blood circulation. Materials and methods: After successful establishment of a diabetic rat model, TPP was administered to diabetic rats for treatment, and the rats were sacrificed at 12 weeks. Retinal electrophysiology and ultrastructures were observed, and serum interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels were also measured. Changes in the retinal expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were examined by immunofluorescence. A mouse model of acute blood stasis was then established, and the effects of TPP on haemorheology were observed. The anti-inflammatory effect of TPP was analysed based on the changes in abdominal capillary permeability and the degree of auricle swelling in the mice. Results: In streptozotocin (STZ)-induced DR rats, TPP (0.4 g/kg) treatment restored electrophysiology indexes and retinal ultrastructures, reduced serum IL-6 and TNF-alpha levels, decreased VEGF and bFGF expression in retinal tissues, and improved haemorheology indexes. Moreover, TPP reduced abdominal capillary permeability and relieved auricle swelling in a dose-dependent manner. Conclusions: TPP treatment ameliorated DR by inhibiting inflammation and improving blood circulation.

The composition of Tongluo Zhujing pill derives from ancient prescription Zhujing pill,and its main function is performed by nourishing liver and kidney, eliminating phlegm and removing blood stasis, and activating channels of eyes to improve eyesight.The main pathogenesis of diabetic optic neuropathy is yin deficiency with blood stasis, and should be treated by invigorating the kidney and nourishing yin, and promoting blood circulation and removing blood stasis,which is exactly consistent with the function of Tongluo Zhujing pill.Primary clinical trials have shown that Tongluo Zhujing pilll has exact therapeutic effectiveness on diabetic reti-nopathy,especially on non-proliferative diabetic retinopathy (NPDR). It can improve eyesight and alleviate pathological changes of retina without toxic and side effect. And the animal studies have proved that Tongluo Zhujing pill has the effects of antioxidation and inhibiting the expression of retinal nuclear factor-kB (NF-kB), which can effectively control the development of diabetic retinopathy.

目的:探讨通络驻景丸对糖尿病(DM)大鼠视网膜病变血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)和内皮素-1(endothelin-1,ET-1)的影响.方法:SPF级SD大鼠,随机取12只,作空白对照组(A组).造模大鼠以剂量为60 mg/kg体质量腹腔注射链脲佐菌素(STZ),将造模成功(72 h后血糖≥16.7 mmol/L)的大鼠随机分为模型对照组(B组)、阳性药(羟苯磺酸钙150 mg/kg)对照组(C组)、通络驻景丸大(3.30 g/kg)、中(1.65 g/kg)、小(0.83 g/kg)剂量组(D组、E组、F组).灌胃给药,24周后,应用放免法测定血清中AngⅡ和ET-1的含量.应用免疫组织化学染色法和实时聚合酶链反应Real-time PCR检测视网膜组织中ET-1 mRNA和ET-1的表达.结果:模型组大鼠血清AngⅡ和ET-1含量比空白对照组升高(P＜0.05),通络驻景丸大、中剂量组和阳性药组比模型组降低(P＜0.05);模型组大鼠视网膜ET-1的含量升高,积分吸光度(IA)与空白对照组相比显著升高(P＜0.05),模型组大鼠视网膜ET-1 mRNA的含量与空白对照组相比显著升高(P＜0.05),通络驻景丸大、中剂量组ET-1和ET-1 mRNA的含量与模型组相比降低并有显著性差异(P＜0.05).结论:通络驻景丸可能通过抑制DM大鼠AngⅡ、ET-1的表达,阻止DM大鼠视网膜病变的发生发展.

The diabetic retinopathy (DR) is deficient root and excessive superficial.Phlegm and blood stasis are the pathological products of diabetis in the process of pathogenesis transformation of Yin deficiency,Qi and yin deficiency,and Yin and Yang deficiency,meanwhile,becoming the new pathogenic factors.Along with diabetes for a long time,phlegm and blood stasis in the collaterals forms syndrome of phlegm and blood stasis resistance blocking collaterals.Tongluo Zhujing Pill was created by LEI Xiaoqin chief physician that was formulated by the materia medica having the function of regulating qi to dissipate dampness as well as dispersing stasis and dredging collaterals based on the formula of Zhujing Pill,showing the curative effect treating syndrome of phlegm and blood stasis blocking collaterals of DR.