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目的:观察氟中毒仔鼠生长发育、学习记忆及血清氧化应激水平的变化情况,探讨氟对仔鼠神经行为发育的作用机制。方法:选择SD大鼠72只(雌雄比例3∶1),适应性喂养1周,按体质量[(80 ± 20)g]采用随机数字表法分为对照组(饮用自来水,含氟量< 0.5 mg/L)、低氟组(饮水含氟量为10.0 mg/L)、高氟组(饮水含氟量为100.0 mg/L),每组24只(雌鼠18只、雄鼠6只),饲养6个月后自由交配产仔;各组母鼠产仔后持续染氟,仔鼠经母乳途径染氟至出生28 d。记录仔鼠的体、脑质量,生长发育指标(张耳、睁眼、牙齿萌出、长毛)和神经行为发育指标(悬崖回避、听觉惊愕、平面翻正、触须定位)的达标时间;出生28 d,采用Morris水迷宫检测仔鼠学习记忆能力(逃避潜伏期)。取出生28 d的仔鼠眼球血,检测血清一氧化氮(NO)含量、一氧化氮合成酶(NOS)及诱导型一氧化氮合成酶(iNOS)活性。结果:出生21、28 d,对照组、低氟组和高氟组仔鼠体质量[21 d:(54.70 ± 3.02)、(52.30 ± 2.58)、(51.30 ± 2.71)g,28 d:(91.70 ± 5.03)、(90.40 ± 4.76)、(86.00 ± 4.55)g]组间比较差异有统计学意义(n F = 3.96、3.70,n P均< 0.05);其中,出生21 d的高氟组仔鼠体质量低于对照组(n P < 0.05);出生28 d的高氟组仔鼠体质量低于对照组和低氟组( n P均< 0.05)。出生28 d,对照组、低氟组和高氟组仔鼠脑质量组间比较差异有统计学意义(n F = 6.19,n P < 0.05);且低氟组和高氟组显著低于对照组( n P均< 0.05)。在生长发育指标中,对照组、低氟组和高氟组仔鼠睁眼完成时间组间比较差异有统计学意义(n F = 3.64,n P < 0.05);且高氟组高于对照组( n P < 0.05)。在神经行为发育指标中,对照组、低氟组和高氟组仔鼠悬崖回避、平面翻正达标时间组间比较差异有统计学意义( n F = 8.29、7.69,n P均< 0.05);且高氟组悬崖回避达标时间高于对照组和低氟组(n P均< 0.05),平面翻正达标时间高于对照组(n P < 0.05)。Morris水迷宫实验第4天,低氟组和高氟组仔鼠逃避潜伏期高于对照组( n P均< 0.05)。血清氧化应激水平结果显示,对照组、低氟组和高氟组仔鼠血清NO含量,NOS、iNOS活性组间比较差异有统计学意义(n F = 4.86、66.48、70.95,n P均< 0.05);且高氟组NO含量高于对照组(n P < 0.05),NOS、iNOS活性高于对照组和低氟组( n P均< 0.05);低氟组血清NOS、iNOS活性高于对照组(n P均< 0.05)。n 结论:过量氟可引起仔鼠血清氧化应激水平升高,可能与仔鼠神经行为发育迟滞、学习记忆能力下降密切相关。“,”Objective:To observe the change of growth and development, learning and memory, and oxidative stress in serum of offspring rats with fluorosis, and to explore the mechanism of fluoride on neurobehavioral development of offspring rats.Methods:Seventy-two SD rats (female and male ratio 3 ∶ 1) were fed adaptively for one week. According to their body mass [(80 ± 20) g], they were divided into control group (drinking tap water, containing less than 0.5 mg/L fluoride), low fluorine group (drinking water containing 10.0 mg/L of fluoride), and high fluorine group (drinking water containing 100.0 mg/L of fluoride) with random number table. After six months of feeding, they mated freely and gave birth in each group (24 rats with 18 females and 6 males). The rats in each group continued to be exposed to fluoride after giving birth, and the offspring rats were exposed to fluoride through breast milk feeding until the 28th day after birth. Body and brain weight, growth and development indicators (auricle separation, eyes opening, teeth eruption and hair growth) and neurobehavioral development indicators (cliff avoidance, auditory startle, surface righting and vibrissa positioning) were recorded. On the 28th day after birth, the learning and memory abilities (escape latency) of offspring rats were tested by Morris water maze; blood samples were taken from eyeballs to detect the content of nitric oxide (NO), the activity of nitric oxide synthase (NOS) and inducible nitric oxide synthase (iNOS).Results:On the 21st day and 28th day after birth, the differences of body weight among control group, low fluorine group and high fluorine group [21st day: (54.70 ± 3.02), (52.30 ± 2.58), (51.30 ± 2.71) g, 28th day: (91.70 ± 5.03), (90.40 ± 4.76), (86.00 ± 4.55) g] were statistically significant (n F = 3.96, 3.70, n P < 0.05); on the 21st day, the body weight of high fluorine group was lower than that of control group ( n P < 0.05); on the 28th day, the body weight of the high fluorine group was lower than those of control group and low fluorine group ( n P < 0.05). On the 28th day, the difference of brain weight of control group, low fluorine group and high fluorine group was statistically significant ( n F = 6.19, n P < 0.05); and the low fluorine group and high fluorine group were lower than that of control group ( n P < 0.05). Among the growth development indicators, the difference of time of completing eyes opening in control group, low fluorine group and high fluorine group was statistically significant ( n F = 3.64, n P < 0.05); and the high fluorine group was higher than that of control group ( n P < 0.05). In neurobehavioral development indicators, the differences of time of completing cliff avoidance, surface righting between the control group, low fluorine group and high fluorine group were statistically significant ( n F = 8.29, 7.69, n P < 0.05); and the time of completing cliff avoidance in high fluorine group was higher than those of control group and low fluorine group ( n P < 0.05), the time of completing surface righting was higher than that of control group ( n P < 0.05). In Morris water maze, on the 4th day, the escape latencies of low fluorine group and high fluorine group were higher than that of control group ( n P < 0.05). The results of oxidative stress in serum showed that there were statistically significant differences in serum NO content, NOS and iNOS activitives between the control group, low fluorine group and high fluorine group ( n F = 4.86, 66.48, 70.95, n P < 0.05); and the NO content of the high fluoirne group was higher than that of the control group ( n P < 0.05), the activities of NOS and iNOS of the high fluoirne group were higher than those of control group and the low fluorine group ( n P < 0.05).n Conclusion:Excessive fluoride can increase the level of oxidative stress in serum, which may be closely related to the neurobehavioral retardation and the decline of learning and memory ability of offspring rats.