异甘草酸镁对紫杉醇致大鼠肝损伤的防治作用及其对血清IL-6、IL-10、TNF-α的影响

doi:10.3877/cma.j.issn.1674-0785.2020.11.014

目的

观察异甘草酸镁（MgIG）对紫杉醇（PTX）致大鼠急性肝损伤的防治作用及对其体内IL-6、IL-10、TNF-α水平的影响。

方法

大鼠50只，采用随机数字表法分成空白组、模型组、MgIG 低剂量组（6.25 mg/kg）、中剂量组（12.5 mg/kg）和高剂量组（25 mg/kg）。MgIG 3个剂量组腹腔注射给药，空白组和模型组给予等体积生理盐水，1次/d，连续腹腔注射给药14 d。除对照组外，其余各组于实验第5天腹腔注射PTX 8 mg/kg建立大鼠肝损伤模型。最后一次给药后24 h，处死大鼠取材，分离血清检测谷丙转氨酶（ALT）、谷草转氨酶（AST）值；ELISA 法检测白介素（IL）-6、IL-10、肿瘤坏死因子（TNF）-α的水平变化；采用HE染色观察各组大鼠肝脏组织病理学改变。

结果

与模型组比较，MgIG低、中、高剂量组大鼠血清ALT［（43.97±7.18）、（42.17±7.67）、（33.63±4.09）U/L vs （52.33±5.63）U/L］和AST［（78.06±5.07）、（75.83±6.45）、（70.40±7.12）U/L vs （86.84±8.72）U/L］水平降低（P＜0.05，P＜0.01，P＜0.001）；与模型组比较，MgIG低、中、高剂量组IL-6［（239.97±13.74）、（236.14±26.12）、（191.34±15.83）ng/L vs （261.02±10.88）ng/L］水平降低（P＜0.05，P＜0.01，P＜0.001），MgIG中、高剂量组IL-10［（30.25±5.25）、（37.06±7.73）pg/ml vs （23.64±2.09）pg/ml］水平升高（P＜0.05，P＜0.001），TNF-α［（70.83±5.91）、（57.83±8.20）ng/L vs （85.27±6.54）ng/L］水平降低（P＜0.01，P＜0.001）。光镜下MgIG 3个剂量组的炎症程度较模型组减轻，并随着剂量增加而减轻程度增加，呈剂量药效关系。

结论

MgIG通过改变大鼠血清促炎因子的水平，并且改善大鼠肝脏病理组织损伤程度，进而对PTX所致大鼠肝损伤起保护作用。

关键词: 异甘草酸镁, 紫杉醇, 急性肝损伤, 细胞因子, 大鼠

Objective

To observe the therapeutic effects of magnesium isoglycyrrhizinate (MgIG) on acute liver injury induced by paclitaxel and its effect on the levels of IL-6, IL-10 and TNF-α in rats.

Methods

Using a random number table method, 50 rats were divided into blank group, model group, MgIG low-dose group (6.25 mg/kg), middle-dose group (12.5 mg/kg) and high-dose group (25 mg/kg). MgIG was given by intraperitoneal injection in 3 dose groups, and the blank group and model group were given equal volume of normal saline, once daily, for 14 days. Except for the control group, the other 4 groups were intraperitoneally injected with paclitaxel 8 mg/kg on the 5th day to establish a rat liver injury model. Rats were sacrificed 24 h after the last administration. Serum was collected to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values. ELISA mathod was used to detect interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) level. HE staining was used to observe histopathological changes in the liver of rats in each group.

Results

The ALT levels of the low, medium and high doses group[(43.97±7.18), (42.17±7.67), (33.63±4.09) U/L] and AST levels [(78.06±5.07), (75.83±6.45), (70.40±7.12) U/L] were significantly lower than those [(52.33±5.63), (86.84±8.72) U/L] of the model group (P＜0.05, P＜0.01 or P＜0.001). IL-6 levels in low, medium and high dose groups [(239.97±13.74), (236.14±26.12), (191.34±15.83) ng/L] and IL-10 levels in middle and high dose groups [(30.25±5.25), (37.06±7.73) pg/ml] were significantly lower/higher than those of the model group [(261.02±10.88) ng/L, (23.64±2.09) pg/ml] (P＜0.05, P＜0.01 or P＜0.001). At the same time, levels of TNF-α [(70.83±5.91), (57.83±8.20) ng/L] in the middle and high dose groups were significantly lower than those in the model group [(85.27±6.54) ng/L] (P＜0.01 or P＜0.001). Under the optical microscope, the degree of inflammation in the three dose groups of MgIG was less than that of the model group, and the degree of reduction increased with the dose.

Conclusion

MgIG can protect the liver damage caused by paclitaxel by changing the level of serum inflammatory factors and improving the degree of liver pathological tissue damage in rats.

Key words: Magnesium isoglycyrrhizinate, Paclitaxel, Acute liver injury, Cytokines, Rats

表1 各组大鼠血清肝功能指标检测结果比较（U/L，

x ˉ

±s）

组别	只数	ALT	AST
空白组	10	35.59±3.62	68.23±7.31
模型组	10	52.33±5.63^a	86.84±8.72^a
低剂量组	10	43.97±7.18^b	78.06±5.07^b
中剂量组	10	42.17±7.67^c	75.83±6.45^c
高剂量组	10	33.63±4.09^d	70.40±7.12^d

表1 各组大鼠血清肝功能指标检测结果比较（U/L，

x ˉ

±s）

组别	只数	ALT	AST
空白组	10	35.59±3.62	68.23±7.31
模型组	10	52.33±5.63^a	86.84±8.72^a
低剂量组	10	43.97±7.18^b	78.06±5.07^b
中剂量组	10	42.17±7.67^c	75.83±6.45^c
高剂量组	10	33.63±4.09^d	70.40±7.12^d

表2 MgIG对大鼠血清中IL-6、IL-10和TNF-α含量变化的影响（

x ˉ

±s）

组别	只数	IL-6（ng/L)	IL-10（pg/ml)	TNF-α（ng/L)
空白组	10	198.35±12.44	42.30±4.39	49.27±7.33
模型组	10	261.02±10.88^a	23.64±2.09^a	85.27±6.54^a
低剂量组	10	239.97±13.74^b	26.08±2.81	77.93±12.03
中剂量组	10	236.14±26.12^c	30.25±5.25^b	70.83±5.91^c
高剂量组	10	191.34±15.83^d	37.06±7.73^d	57.83±8.20^d

表2 MgIG对大鼠血清中IL-6、IL-10和TNF-α含量变化的影响（

x ˉ

±s）

组别	只数	IL-6（ng/L)	IL-10（pg/ml)	TNF-α（ng/L)
空白组	10	198.35±12.44	42.30±4.39	49.27±7.33
模型组	10	261.02±10.88^a	23.64±2.09^a	85.27±6.54^a
低剂量组	10	239.97±13.74^b	26.08±2.81	77.93±12.03
中剂量组	10	236.14±26.12^c	30.25±5.25^b	70.83±5.91^c
高剂量组	10	191.34±15.83^d	37.06±7.73^d	57.83±8.20^d

图1 各组大鼠肝脏病理学改变（HE染色,×400）a为空白组，b 为模型组，c为低剂量组，d 为中剂量组，e为高剂量组

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Therapeutic effect of magnesium isoglycyrrhizinate on liver injury induced by paclitaxel and its effect on serum IL-6, IL-10 and TNF-α

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Therapeutic effect of magnesium isoglycyrrhizinate on liver injury induced by paclitaxel and its effect on serum IL-6, IL-10 and TNF-α