中翻英

甲泼尼龙联合血必净对博莱霉素诱导的肺纤维化
模型干预作用的实验研究
摘    要
目的 观察甲泼尼龙联合血必净对博莱霉素诱导的肺纤维化大鼠血清IL-1β、IL-6、TNF-α含量以及肺组织TGF-β1表达水平的影响，比较甲泼尼龙联合血必净干预博莱霉素诱导的肺纤维化后病理形态学变化，探讨甲泼尼龙联合血必净对肺纤维化的疗效价值及相关作用机制。
方法 将Wister大鼠90只随机分成5组：空白组、模型组、血必净组、甲泼尼龙组及甲泼尼龙血必净联合组。除空白组外，其余4组以气管内滴注博莱霉素（5mg/kg）建立纤维化模型。于造模后第二天起，空白组和模型组每天腹腔注射生理盐水9ml/kg，血必净组每天腹腔注射血必净溶液4.5ml/kg及生理盐水4.5ml/kg，甲泼尼龙组每天腹腔注射1mg/mL的甲泼尼龙溶液4.5ml/kg及生理盐水4.5ml/kg，联合组每天腹腔注射1mg/mL的甲泼尼龙溶液4.5ml/kg及血必净4.5ml/kg，直至第14、28天每组各处死大鼠8只后取材。采用HE及MASSON染色法观察肺组织病理变化，酶联免疫吸附（ELISA）法检测血清IL-1β、IL-6、TNF-α的含量，免疫组织化学染色检测肺组织内TGF-β1的表达水平。
结果
1. 在第14天时间点，血必净组、激素组、联合组与模型组相比较肺泡炎积分明显减小，差异具有显著统计学意义（P<0.01）；在28天时间点，激素组、联合组与模型组相比肺泡炎积分差异仍具有显著统计学意义（P<0.01）。
2. 在第14天时间点，激素组、联合组与模型组相比肺纤维化积分明显减小，与之差异具有统计学意义(p<0.05)，以联合组最为显著（p<0.01）；在28天时间点，血必净组、激素组、联合组与模型组相比肺纤维化积分均有明显下降（p<0.05），但以激素组和联合组积分下降最为显著（p<0.01）。
3. 在第14天时间点，激素组、联合组与模型组相比血清IL-1β含量均有明显下降，与之差异具有统计学意义(p<0.05)，但以联合组下降    更为显著（p<0.01）；在第28天时间点，仅联合组血清IL-1β含量较模型组有明显下降，与之差异有统计学意义（p<0.05）。
4. 在第14天时间点，仅联合组与模型组相比血清IL-6含量有明显下降，与之差异具有统计学意义(p<0.05)；在第28天时间点，血必净组、激素组、联合组血清IL-6含量较模型组均有所下降，但差异无统计学意义（p<0.05）。
5. 在第14天时间点，血必净组、激素组、联合组与模型组相比血清TNF-α含量均有明显下降，与之差异具有统计学意义(p<0.05)，但以联合组下降最为显著（p<0.01）；在第28天时间点，仅有联合组血清TNF-α含量较模型组有明显下降，与之差异具有统计学意义（p<0.05）。
6. 在第14天时间点，激素组、联合组与模型组相比TGF-β1免疫组化图像阳性面积率均有明显下降，与之差异具有统计学意义(p<0.05)；在第28天时间点，血必净组、激素组和联合组TGF-β1免疫组化图像阳性面积率较模型组均有明显减低，与之差异均具有统计学意义（p<0.05），以联合组最为显著（p<0.01）。
结论 甲泼尼龙与血必净联合应用能显著降低博莱霉素诱导的肺间质纤维化大鼠血清IL-1β、IL-6、TNF-α含量，下调肺组织TGF-β1的表达水平，减轻肺组织肺泡炎及肺纤维化程度，从而抑制或延缓博莱霉素致大鼠肺纤维化的发生和发展，对肺纤维化大鼠的保护作用较单一用药效果更为显著。

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Effect of methylprednisolone combining with Xuebijing
Against the bleomycin-induced pulmonary fibrosis
OBJECTIVE To observe the effects of  methylprednisolone combining with Xuebijing on the levels of IL-1β, IL-6, TNF-α in the serum and the expression of TGF-β1 in lung tissue. To investigate the effect of glucocorticoid combining with Xuebijing on the pathological changes of lung tissue.
METHOD Ninty Wister rats were randomly divided into 5 groups: Control group, model group, Xuebijing group, methylprednisolone group and combination group(methylprednisolone combining with Xuebijing). Except the control group, other 4 groups were all exposed bleomycin to set up pulmonary fibrosis rat model by endotracheal injection. After setting up the model, the control group and the model group were intraperitoneally injected saline(9 ml/kg)once a day. The Xuebijing group was injected Xuebijing(4.5ml/kg) and saline(4.5ml/kg). The methylpredn- isolone group was injected methylprednisolone(4.5ml/kg, concentration is 1mg/ml) and saline(4.5ml/kg). And the combination group was injected Xuebijing(4.5ml/kg) and methylprednisolone(4.5ml/kg,concentration is 1mg/ml). Eight rats of each group were sacrificed on day 14 and day 28. Lung injury and pulmonary fibrosis were observed by light microscope. The contents of IL-β1, IL-6 and TNF-α in blood serum were assayed by ELISA. The expressions of TGF-β1 in lung tissue were detected by immunohistochemistry.
RESULT
1. Compared with model group, the degrees of alveolitis in Xuebijing group(p<0.01), methylprednisolone group(p<0.01) and combination group(p<0.01) were decreased significantly on the day 14.And the degrees of alveolitis  in both methylprednisolone group(p<0.05) and combination group(p<0.01) were decreased significantly on the day 28.
2. Compared with model group, the degrees of pulmonary librosis  in both methylprednisolone group(p<0.05) and combination group(p<0.01) were decreased significantly on the day 14. And the degrees of alveolitis in Xuebijing group(p<0.01), methylprednisolone group(p<0.01) and combination group(p<0.01) were decreased significantly on the day 28.
3. Compared with model group, the serum levels of IL-1β in the methylpred- nisolone group(p<0.05) and combination group(p<0.01) were decreased significantly on the day 14. And the serum levels of IL-1β in combination group were decreased significantly on the day 28(p<0.05).
4. Compared with model group, the serum levels of IL-6 in combination group were decreased significantly on the day 14(p<0.05). On the day 28, the serum levels of IL-6  in the Xuebijing group, methylprednisolone group and combination group were all decreased compared with model group, but no statistical significance was found (P>0.05).
5. Compared with model group, the serum levels of TNF-α in Xuebijing group(p<0.05), methylprednisolone group(p<0.05) and combination group(p<0.01) were decreased significantly on the day 14. And the serum levels of IL-1β in combination group(p<0.05) were decreased significantly on the day 28.
6. Compared with model group, the expression of TGF-β1 in both methylprednisolone group(p<0.05) and combination group(p<0.01) were decreased significantly on the day 14. And the expression of TGF-β1  in Xuebijing group (p<0.05), methylprednisolone group(p<0.05) and combination group(p<0.01) were decreased significantly on the day 28.  
CONCLUSION  The combination of glucocorticoid and Xuebijing can decrease    the severity of alveolitis and pulmonary librosis, as well as the serum levels of IL-1β, IL-6 ,TNF-α and TGF-β1 content in lung tissue. The effect was more significant in rats receiving combination of methylprednisolone and Xuebijing in rats than receiving a single drug of glucocorticoid or Xuebijing.
KEY WORDS：bleomycin; pulmonary fibrosis; methylprednisolone; Xuebijing; IL-β1; IL-6; TNF-α; TGF-β1

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