Abstract：
OBJECTIVE: To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats.
METHODS: Twenty-four 70-day-old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey\'s test while the nonparametric data were analysed by the Kruskal-Wallis followed by Dunn\'s test. Significance level was set at 5% (p < .05) for all assessed parameters.
RESULTS: Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05).
CONCLUSIONS: Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.
METHODS: Twenty-four 70-day-old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey\'s test while the nonparametric data were analysed by the Kruskal-Wallis followed by Dunn\'s test. Significance level was set at 5% (p < .05) for all assessed parameters.
RESULTS: Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05).
CONCLUSIONS: Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.
摘要：
目的：评价普萘洛尔全身给药对慢性应激大鼠根尖周炎(AP)严重程度的影响。
方法：24只70日龄雄性Wistar大鼠（Rattusnorvegicus，白化病）分为三组（n=8）：无应激条件的AP大鼠（AP-对照），患有AP并接受慢性不可预测应激（CUS）方案（APS）的大鼠和患有AP并接受普萘洛尔治疗的CUS方案（APSPRO）的大鼠。每天施加应激程序直到实验结束。经过3周的CUS，通过将下颌和上颌第一磨牙的牙髓组织暴露于口腔环境，在所有组中诱导AP。在整个实验期间,每天一次口服给予普萘洛尔治疗。在42天处死大鼠,并通过多重检测收集血液用于应激生物标志物血清剂量。下颌骨被取出并接受显微断层扫描和组织病理学分析。将上第一磨牙周围的根尖组织匀浆并进行RT-PCR分析以评估RANKL的mRNA表达。陷阱和OPG。参数数据使用单向方差分析，然后进行Tukey检验，而非参数数据则通过Kruskal-Wallis分析，然后进行Dunn检验。所有评估参数的显著性水平设定为5%(p<.05)。
结果：Micro-CT显示骨吸收的统计学差异在AP+S组中更大（p<0.05），但对照组和AP+S+PRO组之间无差异(p>.05)。与骨丢失面积较小的AP+S组相比,AP+S+PRO组具有较低的炎症浸润强度和程度(p<0.05)。与对照组相比,应激组AP+S中RANKL和TRAP的基因表达显著增高(p<0.05),与AP+S组相比,在AP+S+PRO中观察到显著更高的OPG表达(p<0.05)。
结论：口服普萘洛尔对应激大鼠的AP严重程度有显著影响，提示在应激动物中对AP的骨吸收具有抗炎作用和保护作用。需要进一步的研究才能充分理解潜在的机制。
方法：24只70日龄雄性Wistar大鼠（Rattusnorvegicus，白化病）分为三组（n=8）：无应激条件的AP大鼠（AP-对照），患有AP并接受慢性不可预测应激（CUS）方案（APS）的大鼠和患有AP并接受普萘洛尔治疗的CUS方案（APSPRO）的大鼠。每天施加应激程序直到实验结束。经过3周的CUS，通过将下颌和上颌第一磨牙的牙髓组织暴露于口腔环境，在所有组中诱导AP。在整个实验期间,每天一次口服给予普萘洛尔治疗。在42天处死大鼠,并通过多重检测收集血液用于应激生物标志物血清剂量。下颌骨被取出并接受显微断层扫描和组织病理学分析。将上第一磨牙周围的根尖组织匀浆并进行RT-PCR分析以评估RANKL的mRNA表达。陷阱和OPG。参数数据使用单向方差分析，然后进行Tukey检验，而非参数数据则通过Kruskal-Wallis分析，然后进行Dunn检验。所有评估参数的显著性水平设定为5%(p<.05)。
结果：Micro-CT显示骨吸收的统计学差异在AP+S组中更大（p<0.05），但对照组和AP+S+PRO组之间无差异(p>.05)。与骨丢失面积较小的AP+S组相比,AP+S+PRO组具有较低的炎症浸润强度和程度(p<0.05)。与对照组相比,应激组AP+S中RANKL和TRAP的基因表达显著增高(p<0.05),与AP+S组相比,在AP+S+PRO中观察到显著更高的OPG表达(p<0.05)。
结论：口服普萘洛尔对应激大鼠的AP严重程度有显著影响，提示在应激动物中对AP的骨吸收具有抗炎作用和保护作用。需要进一步的研究才能充分理解潜在的机制。
