大鼠长期摄入低浓度溴氰菊酯致胃黏膜组织损伤的实验研究
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摘要
背景资料：溴氰菊酯(deltamethrin,DM)是Ⅱ拟除虫菊酯类(Synthetic pyrethroids,SPs)杀虫剂,是人工合成拟除虫菊酯杀虫剂中杀虫毒力最大的一个品种。此类药物在人体内易被氧化酶系统降解,无蓄积性,被认为是毒性较低,使用安全的农药。主要用以防治棉田、菜地、果树、茶叶等害虫。市面上出售的大多数蚊香、喷雾杀虫剂、灭蟑螂药都是拟除虫菊酯类农药。
随着SPs的广泛使用,常因使用不当或污染食品而引起中毒,其所引起的环境问题倍受人们的关注,特别是拟除虫菊酯类农药是一种神经毒剂,作用于神经膜,改变神经膜的通透性,干扰神经传导而产生中毒。溴氰菊酯对哺乳动物的毒性主要表现在中枢神经系统,突出症状表现为：流涎震颤。有关溴氰菊酯毒理方面的研究和评价已有大量文献报道,突出体现在对高等动物和鱼类等水生生物的急性毒性、亚急性毒性。
目的：探索溴氰菊酯慢性中毒对大鼠胃黏膜的病理损伤、机制及P物质的表达和意义。
方法：清洁级Wistar大鼠32只,雌雄各半,体重120-150g,购于青岛市实验动物中心。随机分成4组,每组8只。实验组大鼠分别给予不同剂量溴氰菊酯即低剂量组1.5625 mg/kg；中剂量组3.1250 mg/kg；高剂量组6.2500 mg/kg；溶剂为橄榄油,对照组仅给予橄榄油。给予量均按照大鼠5mL/kg计算。每日9：00进行灌胃,每周连续灌胃5天,共持续24周。每周灌胃前测量各组大鼠体重。大鼠处死前禁食24 h,以8%水合氯醛(5ml/kg)腹腔麻醉后,取胃体部组织,制成石蜡切片,HE染色及免疫组织化学技术染色,镜下观察胃黏膜组织的损伤及胃黏膜组织中P物质的表达情况,并对胃黏膜组织的损伤程度进行累计积分、胃底腺壁细胞计数。
结果：对照组大鼠,镜下见胃黏膜组织结构完整,胃底腺排列紧密规则,壁细胞形态结构正常,无炎性细胞浸润。实验组大鼠与对照组大鼠相比较,胃黏膜组织均呈现不同程度的损伤,有剂量-效应关系。高剂量组大鼠胃黏膜慢性损害的病理积分与各组相比差异均有显著性(P<0.05)；胃底腺壁细胞计数与对照组相比较其差异有统计学意义(P<0.05)。免疫组化发现SP在实验组大鼠胃黏膜组织中呈强阳性表达,在对照组则呈弱阳性表达；平均光密度(OD)值显示：高、中剂量组之间及与其余各组之间差异均有显著性(P<0.05)。
结论：大鼠长期摄入低浓度溴氰菊酯对其胃黏膜组织有较明显的损伤作用,尤其对胃底腺壁细胞的影响较为明显,表现为壁细胞数量因中毒剂量的不同而改变,高剂量组壁细胞的数量高于中剂量组、低剂量组、对照组,且与对照组相比有统计学意义。对大鼠胃黏膜组织损伤的机制可能与胃黏膜屏障的破坏、胃黏膜血流量的减少及胃肠激素的变化有关,其中P物质可能参与胃黏膜局部病变的过程。
Background:Deltamethrin (deltamethrin, DM) belonging to the type ofⅡpyrethroid (Synthetic pyrethroids, SPs) insecticide, is one of the largest toxicity pesticides in the synthetic pyrethroid insecticide controlling pests in cotton, vegetable, fruit, tea and mothes in experiment samples. It is considered low toxic and more safe pesticides because of it is susceptible to degradate by enzyme system and no accumulation. Most mosquito repellents,air freshener and cockroachkillers are pyrethroid pesticides.
With the SPs widely using, it was concerned in poison by mis-use or polluting food causing environment problems, especially it is a nerve toxic activity that it can act on the nerve membrane, change permeability of the nerve membrane and disturbance the nerve conduction. The toxicity of deltamethrin is mainly on the central nervous system of the mammalian and their important toxic symptoms are:tremor and salivation. The study about the toxicity of deltamethrin refer to the acute and subacute toxicity on the mammalian and aquatic animal (i.e.fish).
Object: To explore the chronic toxicity of deltamethrin on rats gastric mucosa injury and expression of substance P in the gastric mucosa.
Methods:Wistar rats (No.=32), male and female, weighting 120g-150g (Laboratory Animal Center,Qingdao)were randomly divided four groups and each group contained eight rats. Wistar rats were given different doses of deltamethrin dissolved in the olive oil via esophagus: low-dose group(1.5625 mg/kg), mid-dose group(3.1250 mg/kg), high-dose group(6.2500 mg/kg), but the control group received olive oil only. The dosage of standard was 5ml/kg. DM dissolved in olive oil was administered to rats through esophagus at AM 9:00 every day, for 24 weeks. The body weight was measured every week before administration of DM. Twenty-four weeks later, rats fasted overnight were anaesthetized with 8% Chloral Hydrate (5ml/kg). Paraffin sections were made from the fundus of stomach. After HE and immunohistochemical staining, the degrees of gastric mucosa injury and the expression of substance P were observed.
Results:Gastric mucosa of the control group was looked normal and integrated, fundic glands was regular, parietal cells were normal and no inflammation cells were found by light microscopic observation. However, gastric mucosa of deltamethrin treated rat shown different degrees of lesions on the basis of different dosages. Compared with those of other groups, the degrees of gastric mucosa damage in high-dose group were notably higher (P<0.05) and the number of parietal cells in high-dose group was significantly higher too (P<0.05). Expression of substance P was found in cells of the rat gastric mucosa in all groups with the weak expression found in the control group. The average optical density (OD) values found in the high and middle dose groups were significantly higher than those of another groups (P<0.05).
Conclusion:Deltamethrin has apparently chronic harmful effects on rats'gastric mucosa injury especially the number of the parietal cells in the fundic gland is increasing according to the different of dosage. The number of the parietal cells in the high group is higher than the another group, and compared the control group the number of the parietal cells is significant on satistics. The mechanisms may be relate to the damage of stomach mucosa barrier、gastric mucosal blood flow、the changes of hormone in stomach and SP may be involved in the pathogenesis of the localized gastric lesions.
随着SPs的广泛使用,常因使用不当或污染食品而引起中毒,其所引起的环境问题倍受人们的关注,特别是拟除虫菊酯类农药是一种神经毒剂,作用于神经膜,改变神经膜的通透性,干扰神经传导而产生中毒。溴氰菊酯对哺乳动物的毒性主要表现在中枢神经系统,突出症状表现为：流涎震颤。有关溴氰菊酯毒理方面的研究和评价已有大量文献报道,突出体现在对高等动物和鱼类等水生生物的急性毒性、亚急性毒性。
目的：探索溴氰菊酯慢性中毒对大鼠胃黏膜的病理损伤、机制及P物质的表达和意义。
方法：清洁级Wistar大鼠32只,雌雄各半,体重120-150g,购于青岛市实验动物中心。随机分成4组,每组8只。实验组大鼠分别给予不同剂量溴氰菊酯即低剂量组1.5625 mg/kg；中剂量组3.1250 mg/kg；高剂量组6.2500 mg/kg；溶剂为橄榄油,对照组仅给予橄榄油。给予量均按照大鼠5mL/kg计算。每日9：00进行灌胃,每周连续灌胃5天,共持续24周。每周灌胃前测量各组大鼠体重。大鼠处死前禁食24 h,以8%水合氯醛(5ml/kg)腹腔麻醉后,取胃体部组织,制成石蜡切片,HE染色及免疫组织化学技术染色,镜下观察胃黏膜组织的损伤及胃黏膜组织中P物质的表达情况,并对胃黏膜组织的损伤程度进行累计积分、胃底腺壁细胞计数。
结果：对照组大鼠,镜下见胃黏膜组织结构完整,胃底腺排列紧密规则,壁细胞形态结构正常,无炎性细胞浸润。实验组大鼠与对照组大鼠相比较,胃黏膜组织均呈现不同程度的损伤,有剂量-效应关系。高剂量组大鼠胃黏膜慢性损害的病理积分与各组相比差异均有显著性(P<0.05)；胃底腺壁细胞计数与对照组相比较其差异有统计学意义(P<0.05)。免疫组化发现SP在实验组大鼠胃黏膜组织中呈强阳性表达,在对照组则呈弱阳性表达；平均光密度(OD)值显示：高、中剂量组之间及与其余各组之间差异均有显著性(P<0.05)。
结论：大鼠长期摄入低浓度溴氰菊酯对其胃黏膜组织有较明显的损伤作用,尤其对胃底腺壁细胞的影响较为明显,表现为壁细胞数量因中毒剂量的不同而改变,高剂量组壁细胞的数量高于中剂量组、低剂量组、对照组,且与对照组相比有统计学意义。对大鼠胃黏膜组织损伤的机制可能与胃黏膜屏障的破坏、胃黏膜血流量的减少及胃肠激素的变化有关,其中P物质可能参与胃黏膜局部病变的过程。
Background:Deltamethrin (deltamethrin, DM) belonging to the type ofⅡpyrethroid (Synthetic pyrethroids, SPs) insecticide, is one of the largest toxicity pesticides in the synthetic pyrethroid insecticide controlling pests in cotton, vegetable, fruit, tea and mothes in experiment samples. It is considered low toxic and more safe pesticides because of it is susceptible to degradate by enzyme system and no accumulation. Most mosquito repellents,air freshener and cockroachkillers are pyrethroid pesticides.
With the SPs widely using, it was concerned in poison by mis-use or polluting food causing environment problems, especially it is a nerve toxic activity that it can act on the nerve membrane, change permeability of the nerve membrane and disturbance the nerve conduction. The toxicity of deltamethrin is mainly on the central nervous system of the mammalian and their important toxic symptoms are:tremor and salivation. The study about the toxicity of deltamethrin refer to the acute and subacute toxicity on the mammalian and aquatic animal (i.e.fish).
Object: To explore the chronic toxicity of deltamethrin on rats gastric mucosa injury and expression of substance P in the gastric mucosa.
Methods:Wistar rats (No.=32), male and female, weighting 120g-150g (Laboratory Animal Center,Qingdao)were randomly divided four groups and each group contained eight rats. Wistar rats were given different doses of deltamethrin dissolved in the olive oil via esophagus: low-dose group(1.5625 mg/kg), mid-dose group(3.1250 mg/kg), high-dose group(6.2500 mg/kg), but the control group received olive oil only. The dosage of standard was 5ml/kg. DM dissolved in olive oil was administered to rats through esophagus at AM 9:00 every day, for 24 weeks. The body weight was measured every week before administration of DM. Twenty-four weeks later, rats fasted overnight were anaesthetized with 8% Chloral Hydrate (5ml/kg). Paraffin sections were made from the fundus of stomach. After HE and immunohistochemical staining, the degrees of gastric mucosa injury and the expression of substance P were observed.
Results:Gastric mucosa of the control group was looked normal and integrated, fundic glands was regular, parietal cells were normal and no inflammation cells were found by light microscopic observation. However, gastric mucosa of deltamethrin treated rat shown different degrees of lesions on the basis of different dosages. Compared with those of other groups, the degrees of gastric mucosa damage in high-dose group were notably higher (P<0.05) and the number of parietal cells in high-dose group was significantly higher too (P<0.05). Expression of substance P was found in cells of the rat gastric mucosa in all groups with the weak expression found in the control group. The average optical density (OD) values found in the high and middle dose groups were significantly higher than those of another groups (P<0.05).
Conclusion:Deltamethrin has apparently chronic harmful effects on rats'gastric mucosa injury especially the number of the parietal cells in the fundic gland is increasing according to the different of dosage. The number of the parietal cells in the high group is higher than the another group, and compared the control group the number of the parietal cells is significant on satistics. The mechanisms may be relate to the damage of stomach mucosa barrier、gastric mucosal blood flow、the changes of hormone in stomach and SP may be involved in the pathogenesis of the localized gastric lesions.
引文
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