EPO对唾液腺放射性损伤防护作用的研究

目的:通过研究促红细胞生成素(Erythropoietin,EPO)对大鼠下颌下腺放射性损伤的防护作用,为临床进一步探索唾液腺放射性损伤的预防和保护提供实验基础。 方法:将30只Wistar大鼠平均分为3组,即对照组(模拟照射+注射盐水)、单放组(照射+注射盐水)、给药组(照射+注射药物)。大鼠头颈部一次性接受15 Gy大剂量放射线照射,给药组放射前30 min腹腔注射EPO,照射后隔日给药,持续2周,药物剂量为每次3000 IU/kg。放射后第90天测量大鼠唾液流率,测量完毕后取大鼠颌下腺制作石蜡切片,行HE染色、Masson染色,并通过免疫组织化学染色观察切片PCNA表达情况。结果:给药组大鼠唾液流率大于单放组,组织学观察给药组腺体损伤程度较单放组明显减轻,每高倍视野(×400)给药组PCNA阳性细胞数多于单放组。结论:EPO对唾液腺放射性损伤有较好的防护作用。     

单一剂量单侧腮腺放射损伤对双侧腮腺结构和功能的影响

目的 研究单一大剂量射线照射单侧小型猪腮腺对双侧腮腺结构和功能影响。方法 14只小型猪一侧腮腺用直线加速分别给予15 Gy（7只）和20 Gy（7只）离子射线照射,4只做为空白对照。分别在放射前,放射后4周和16周观察腮腺唾液流率、腺体重量、腺泡面积和组织学变化。结果 4周时,15 Gy和20 Gy照射后放射侧腮腺重量下降达50%;15 Gy照射后放射侧腮腺唾液流率无明显下降,20 Gy照射后放射侧腮腺唾液流率减少约50％。16周时,15 Gy和20 Gy照射后放射侧腮腺重量下降达50%,组织学明显改变,照射后放射侧腮腺流率分别下降约60%及80%。非放射侧腮腺重量及形态均无明显变化,但20 Gy照射后16周时非放射侧腮腺唾液流率明显下降。结论 单一剂量照射后腮腺结构的改变相对唾液流率下降发生较早,唾液流率减少与腺泡面积的减少不完全成正相关。非照射侧腮腺形态变化不明显,但唾液流率明显下降。     

电离辐射对大鼠颌下腺形态及功能的影响

目的：观察电离辐射对大鼠颌下腺形态及功能的影响。方法：一次性15Gy X射线局部照射大鼠唾液腺区，观察照射后30天内动物体重、颌下腺重量、毛果芸香碱的潜伏期（lag phase)、唾液流率、电解质、组织学等变化。结果：照射后大鼠体重及颌下腺重量减轻，唾液流率降低，Na^ 降低、K^ 升高，Ca^2 变化不显著、毛果芸香碱的潜伏期延长。早期主要是细胞形态结构的变化，晚期主要是唾液腺实质细胞萎缩，数量减少。结论：照射后大鼠颌吓腺发生了形态变化及不可逆性功能障碍。卷曲颗粒导管（CGT）细胞是靶细胞。     

吲哚美辛通过抑制COX-2表达影响颌骨骨折愈合

建立SD大鼠双侧下颌骨颊舌向贯穿的不完全骨折实验动物模型,20只SD大鼠随机分为吲哚美辛给药组与生理盐水对照组。术后连续给药5d,分别于给术后6、8、11、15、22d处死大鼠并取双侧下颌骨,进行HE染色,总胶原特殊染色及免疫组化染色,并进行对比观察。结果:组织学观察结果显示实验组早期炎症细胞减少,骨小梁出现时间延迟,在早期实验组总胶原明显低于对照组,但后期未见明显差     

电离辐射对大鼠颌下腺TNFα和FGF2表达的影响

目的:观察照射后大鼠颌下腺TNFα和FGF2的表达变化,探讨放疗后唾液腺纤维化的可能分子机制。方法 :19只大鼠随机分为对照组(只麻醉不照射)、照射组。照射组用15 Gy的X射线进行颌下腺区局部照射1次,照射后3 d和30 d处死大鼠取颌下腺,4%多聚甲醛固定、石蜡包埋、切片,免疫组化染色观察颌下腺TNFα和FGF2表达的变化。结果:照射后3 d和30 d大鼠颌下腺TNFα和FGF2表达均升高,30 d组高于3 d组。结论:照射后唾液腺纤维化可能与TNFα和FGF2表达升高有关。     

大鼠腮腺及颌下腺唾液的收集

目的:探讨大鼠腮腺及颌下腺唾液的收集方法。方法:采用微型Lashley吸盘法收集大鼠腮腺唾液,经口内颌下腺导管口直接插管法收集颌下腺唾液。毛果芸香碱刺激唾液分泌,假设唾液的比重为1.0 g/cm3,以唾液重量代表其体积,记录唾液流率。结果:大鼠腮腺唾液流率(9.9±1.4)μL/m in,颌下腺导管插管唾液流率(19.9±10.8)μL/m in。结论:可以采用微型吸盘法收集大鼠腮腺唾液,经口内颌下腺导管口直接插管法收集大鼠颌下腺唾液。     

放疗对小型猪腮腺颌下腺舌下腺微血管损伤影响的实验研究

目的:观察放疗对小型猪腮腺、颌下腺、舌下腺的微血管损伤状况。方法:将6只实验用小型猪分为2组。2组动物进行放疗,将双侧腮腺、颌下腺、舌下腺加入放射野中,放疗组20Gy/每侧,对照组0Gy/每侧。放疗结束后4 h处死两组动物,取两组动物腮腺、颌下腺、舌下腺标本行HE染色与CD31免疫组化染色,观察放疗早期3种腺体微血管密度变化。结果:两组小型猪腮腺、颌下腺、舌下腺CD31阳性染色颗粒数有显著差异(P＜0.05);3个腺体间统计结果有显著性差异(P＜0.05);腮腺与颌下腺及舌下腺有显著性差异(P＜0.05),颌下腺与舌下腺无显著性差异。结论:放疗可导致小型猪腮腺、颌下腺、舌下腺微血管密度明显减低,且各腺体间微血管密度减低有差异,腮腺的损伤程度大于颌下腺和舌下腺。     

失副交感神经支配对大鼠颌下腺分泌功能的影响

目的观察大鼠颌下腺失副交感神经支配后近远期分泌功能的变化,探讨失副交感神经支配调控颌下腺分泌、治疗口干的可能性。方法将20只雄性成年SD大鼠分为实验组（12只）和正常对照组（8只）。实验组行右侧鼓舌神经切除术,实验组左侧及正常对照组颌下腺均未处理。术后1、12和24周采用希尔默试验（Schirmer test）检测颌下腺的分泌功能。结果 进食刺激状态下实验组手术侧腺体的唾液流率明显低于非手术侧[(27.13±3.28)、(33.00±12.98)和(27.50±5.20) mm]和正常对照组[(30.25±3.86)、(28.00±3.46)和(27.00±4.32) mm](P＜0.05),证实术后颌下腺失去副交感神经支配。但在静息状态下,术后各时间点实验组手术侧腺体的唾液流率显著高于非手术侧[(1.91±0.62)、( 1.33±0.29)和(2.38±1.79) mm]和正常对照组[(1.90±0.34)、(1.53±0.46)和(1.48±0.39) mm](P＜0.05);非手术侧与正常对照组腺体唾液流率的差异无统计学意义。结论采用颌下腺失副交感神经支配治疗口干有一定的可能性。     

Rad50在放射后大鼠涎腺中的表达

目的:检测Rad50在放射后大鼠涎腺组织中的表达水平。方法:选用60只Wistar大白鼠,随机分成6组,每组10只。分为对照组(未照射)、3 Gy组、6 Gy组、9 Gy组、12 Gy组、15 Gy组。放射组大白鼠用60Co一次性照射后2 h内处死,立即取出其腮腺、下颌下腺组织备用。用电镜观察放射后各组涎腺组织超微结构的变化,用反转录聚合酶链反应(RT-PCR)检测Rad50基因表达水平的变化,用免疫组织化学法观察其蛋白表达水平的变化。结果:各放射组涎腺组织中Rad50的表达均高于对照组(P<0.05),但不同放射剂量的各放射组之间Rad50的表达无明显差异(P>0.05)。透射电镜下可见大鼠腮腺、下颌下腺细胞超微结构随着放射剂量的增加,发生较明显改变。结论:放射可引起涎腺组织Rad50表达水平增高,但其表达水平并未随放射剂量的增加而增高,提示Rad50在涎腺放射损伤修复中的表达水平有限,这可能是涎腺放射敏感性机制之一。     

小型猪腮腺放射损伤唾液流率和血常规及生化动态观察

目的 :动态观察小型猪腮腺放射损伤前后腮腺流率、血常规及血生化变化 ,为建立小型猪腮腺放射损伤动物模型 ,及基因治疗涎腺放射损伤奠定基础。方法 :试验组 8只小型猪 ,1 5Gy单侧腮腺放射损伤 ,对侧腮腺做对照 ,2只 0Gy放射做空白对照。放疗前、放疗后 4周、8周和 1 6周 ,用吸盘法收集唾液 ,前腔静脉取血 ,观察唾液流率、血常规和血生化改变。结果 :放疗后 8周唾液流率下降 ,1 6周唾液流率下降明显并与放疗前有显著性差别。随着放射后的时间延长 ,白细胞计数下降越来越明显 ,第 8周和 1 6周与放疗前有显著性差别。红细胞在放疗后第 8周及第 1 6周稍有增加但没有显著性差别 ,血小板在 4周下降 ,第 8周及第 1 6周增高超出放射前水平。乳酸脱氢酶血清含量放疗后呈持续下降趋势 ,与放疗前有显著性差别(P <0 0 5 )。血清淀粉酶在放疗后 1周增高 ,第 4周显著下降 ,与放疗前相比差别有显著性 ,随后缓慢回升。结论 :1 5Gy放疗1 6周时放疗侧腮腺唾液流率明显下降 ,血液常规白细胞计数和血清乳酸脱氢酶、淀粉酶改变     

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目的    观察糖尿病大鼠腮腺、颌下腺、舌下腺超微结构变化。方法    雄性Wistar大鼠20只,随机分对照组和实验组,各10只。实验组：腹腔注射四氧嘧啶制作糖尿病大鼠模型;对照组：正常饲养。动物模型建成后第8周时称重并测定各组大鼠空腹血糖,然后取材制片,应用透射电镜观察大鼠腮腺、颌下腺、舌下腺超微结构变化。结果    建模后第8周时对照组大鼠体重（282.40±14.00）g,血糖（5.50±0.40）mmol／L;实验组大鼠体重 （148.45±8.45）g,血糖（25.20±4.10）mmol／L,组间比较差异有统计学意义（P < 0.05）。实验组大鼠腮腺细胞细胞核轮廓不规则,线粒体肿胀,粗面内质网扩张;颌下腺细胞细胞核固缩,线粒体出现空泡变性、嵴断裂;舌下腺细胞未见明显改变。结论    糖尿病可导致腮腺和颌下腺分泌功能受损而出现口干症状,但未影响舌下腺功能,舌下腺可能起到一定的代偿作用。     

黄芪丹参对干燥综合征模型大鼠颌下腺组织的水通道蛋白-5表达的影响

目的 探讨黄芪合并丹参对干燥综合征模型大鼠颌下腺组织水通道蛋白-5(AQP5)的影响。方法 自身同种鼠抗原合并百白破疫苗加强免疫法免疫模型动物;用Western blot分析SS大鼠颌下腺AQP5表达的影响。结果 免疫动物出现类似SS的病理改变,存在大量淋巴细胞浸润,提示免疫造模成功。Western blot检测显示各组均出现分子量为42 KD的条带。空白对照组AQP5表达值正常(1.35±0.13),造模生理盐水组AQP5表达值(1.03±0.08)明显减少,造模中药高剂量组AQP5表达值较造模生理盐水组明显增强(1.31±0.15)。与空白对照组比较,造模生理盐水组AQP5表达显著减少(P<0.05);与造模生理盐水组比较造模中药高剂量组AQP5有表达显著增加(P<0.01)。结论 唾液流量的增加、颌下腺指数降低提示中药黄芪、丹参有改善唾液腺分泌唾液的功能;Western blot检测显示黄芪、丹参通过增强颌下腺水分子通道的释放,上调AQP5的表达,扩大颌下腺水分子的滤过,缓解口腔干燥的症状。?     

Structural and functional injury in minipig salivary glands following fractionated exposure to 70 Gy of ionizing radiation: an animal model for human radiation-induced salivary gland injury

This study explored the feasibility of developing an animal model for radiation-induced salivary gland injury with a radiation protocol identical to current clinical practice. Three male Hanford minipigs were subjected to fractionated daily irradiation with a total dose of 70 Gy; structural and functional measures were compared with those of a control group of minipigs. We found that irradiated submandibular and parotid glands were one-third to one-half the gross size of control glands. Whereas no pathologic changes were noted in control glands, irradiated glands consistently demonstrated significant parenchymal loss with extensive acinar atrophy and interstitial fibrosis, enlarged nuclei in remaining acinar cells, and ductal dilatation and proliferation. Stimulated salivary flow was reduced by 81% in irradiated animals compared with preirradiation flow (P <.001); salivary flow in the control group increased by 30% during the same period (P <.001). The observed radiation-induced structural and functional salivary gland changes are comparable in every respect to those observed following irradiation of human salivary glands.     

A comparative study of the role of atresia and stenosis of the outflow duct of a salivary gland in the pathogenesis of dystrophic and inflammatory changes]

Experiments were carried out with submandibular salivary glands of 20 dogs. Complete obturation of the submandibular duct (in 10 animals) was achieved by binding this duct. Partial impairment of the saliva flow from the gland was induced in 10 animals by fixing a metal ring on the duct. The experiment has demonstrated that both complete and partial obturation of the salivary duct result in the development of chronic sialadenitis. Partial obturation of salivary outflow from the gland did not result in an acute inflammation but in a flaccid process, slowly developing dystrophic changes in acinar cells, gradually developing sclerosis of the glandular parenchyma and stroma. These data indicate a direct relationship between the intensity of dystrophic changes in the salivary gland and the severity of impairment of salivary discharge.     

The effect of X-ray irradiation on the function and saliva composition of rat parotid and submandibular/ sublingual glands

Radiation therapy to the head and neck area frequently causes severe salivary gland dysfunction and xerostomia. Morphological studies of irradiated salivary glands have suggested that the submandibular/sublingual gland may be less radiosensitive than the parotid gland. The purpose of this study was to evaluate the effect of radiation on major salivary gland functions in rats with radiation-induced xerostomia. The effect of salivary gland irradiation on salivary function was examined in specific pathogen-free Sprague-Dawley rats. The animals were irradiated with a single exposure of either 22 Gy or 32 Gy. Stimulated saliva excretion time was measured for the parotid and submandibular/ sublingual glands, and the total protein in saliva was analysed. Our results showed that the saliva flow rate and protein concentration of parotid saliva were significantly reduced in the 32 Gy-irradiated rats.     

The effect of food consistency and dehydration on reflex parotid and submandibular salivary secretion in conscious rats

Changes in salivary secretion with different consistency of diet and dehydration were studied in male Wistar rats under unrestricted conditions. To measure the salivary secretion, a stop-flow method was used. There was little unstimulated salivary secretion from the parotid and submandibular glands, but eating solid, powdered, and liquid diets induced parotid and submandibular saliva. There was no significant change in the volume and flow rate of saliva in bilateral parotid glands during the eating of solid diets. The solid and powdered diets induced significantly more salivary secretion from the parotid gland than did the liquid. The salivary flow rate with solid diets was significantly greater from the parotid gland than from the submandibular. On the other hand, the salivary flow rate with the liquid diet was significantly smaller from the parotid gland than from the submandibular. Appreciable amounts of submandibular saliva, but little parotid saliva were secreted during grooming. Clearly, parotid and submandibular saliva have different roles in the rat. When injected intraperitoneally with 1.5 M NaCl solution or water-deprived for 24 h, rats took longer to eat the solid diets, and had increased salivary volume and decreased flow rate from the parotid gland. These results indicate that the moisture content of the diet and the dryness of the mouth alters the volume of parotid saliva secreted in rats and show that parotid saliva plays an important part in mastication and swallowing.     

Physostigmine-induced salivary secretion in the rat

The purpose of this study was to see if physostigmine, a reversible cholinesterase inhibitor, affects the secretion and composition of saliva of the major salivary glands of the rat. Low doses of physostigmine did not elicit secretion. At higher doses there was significant flow from the parotid and submandibular glands within 5 min; however, no sublingual secretion was observed. The submandibular flow rate was highest for the first 5 min, then declined rapidly. The parotid flow rate initially was one-fifth of the maximum submandibular rate and then gradually decreased. The concentrations of Ca, Na and K of physostigmine-induced parotid saliva, and the Na of submandibular saliva, were similar to those with carbachol stimulation. The Ca and K concentrations of submandibular saliva were significantly higher than with carbachol or parasympathetic stimulation, and resembled those of alpha-adrenergic stimulation. The protein concentrations of physostigmine-evoked saliva from both glands were similar. The amylase activity of physostigmine-evoked parotid saliva was much higher than that of carbachol or parasympathetic stimulation. Physostigmine-evoked secretion was completely blocked by atropine, a cholinergic antagonist, and by reserpine, partially blocked by phentolamine, an alpha-adrenergic antagonist and not affected by surgical sympathectomy. Morphologically, physostigmine resulted in a moderate decrease in the number of acinar, but not ductal, secretory granules of both the parotid and submandibular glands, while the sublingual gland was unaffected. Numerous patches of parotid acini also developed vacuoles or vesicles. These results suggest that physostigmine-induced salivary secretion is mediated primarily by direct effects on cholinergic and alpha-adrenergic receptors.     

Effect of ionizing radiation on sympathetic nerve function in rat parotid glands

Ionizing radiation (IR) irreversibly damages salivary glands. The pathologic mechanism is unknown. Previously we reported that parotid serous acinar cells may not be the primary site of damage by IR. The purpose of this study was to determine if IR alters sympathetic nerve function in rat parotid glands. Male adult rats received a single dose of radiation (20 Gy) to the head and neck. Three days after IR, parotid saliva secretion induced by norepinephrine (NE) was completely blocked. Catecholamine uptake and metabolism were studied by injecting [3H] dopamine ([3H]DA) into irradiated rats, as a bolus. After 60 min, animals were sacrificed and the parotid gland, submandibular gland, and left ventricle removed. Tissue contents of [3H]DA and [3H]NE, identified by HPLC, were unaffected by IR. The results indicate that IR abolishes acinar responsiveness to NE without affecting parotid sympathetic nerve function.