Gao Yuan, Song Lin-Xuan, Jiang Miao-Na, Ge Guang-Yan, Jia Yu-Jie
Dalian Medical University, Dalian, Liaoning 116044, China.
Inflammation. 2008 Apr;31(2):121-32. doi: 10.1007/s10753-008-9057-3. Epub 2008 Feb 27.
The aim of this research is to study the effects of traditional Chinese medicine on endotoxin and its receptors in rats with nonalcoholic steatohepatitis (NASH).
Fifty-six SD rats were divided into seven groups. All the animals were fed high fatty diet for 12 weeks. Rats with non-alcoholic steatohepatitis (NASH) were treated with traditional Chinese medicine according to low-dose, middle-dose, high-dose and Lipitor from fifth week. All rats were killed at the end of 12th week. The liver pathology changes were observed under light microscope. The levels of serum lipoid, alanine aminotransferase (ALT), endotoxin (ET), tumor necrosis factor-alpha (TNF-alpha) and interleukine-1beta (IL-1beta) were determined. The expressions of CD14 and nuclear transcriptional factor kappaB (NF-kappaB) were observed by immunohistochemistry. The expressions of lipopolysaccharide binding protein (LBP), toll-like receptor-4 (TLR-4), myeloid differentiation-2 (MD-2) and induced nitric oxide synthase (iNOS) mRNA were detected by the reverse transcription polymerase chain reaction (RT-PCR).
The levels of serum endotoxin in the middle dose group (0.0225 +/- 0.0112 EU/l) were lower than those in high fatty diet model group (0.2249 +/- 0.0982 EU/l) at 12th week, the difference was significant (P < 0.01). In the middle dose group, mean values of serum TNF-alpha and IL-1beta levels decreased dramatically (1.604 +/- 0.302 ng/ml and 0.052 +/- 0.024 ng/ml) compared with those in the high fatty diet model group (4.029 +/- 1.180 ng/ml and 14.944 +/- 0.491 ng/ml; P < 0.01 and P < 0.01). The expressions of CD14 and NF-kappaB in the middle dose group decreased compared with those in the high fatty diet model group. The expressions of LBP mRNA (0.284 +/- 0.105) and TLR-4 mRNA (0.290 +/- 0.123) in the middle dose group down regulated compared with those in the high fatty diet model group (1.060 +/- 0.158 and 1.261 +/- 0.368; P < 0.01 and P < 0.01). In the middle dose group MD-2 and iNOS gene expressions were 0.132 +/- 0.058 and 0.164 +/- 0.061, respectively, which were significantly lower compared with the high fatty diet model group (0.795 +/- 0.294 and 1.029 +/- 0.388; P < 0.01 and P < 0.01).
The mechanism of non-alcoholic steatohepatitis (NASH) maybe related to increasing the levels of serum endotoxin, upregulating endotoxin receptors of hepatic tissue and enhancing liver inflammatory injury. Traditional Chinese medicine is a good treatment for non-alcoholic steatohepatitis (NASH). It can produce a marked effect via relieving LPS-induced liver injury.
本研究旨在探讨中药对非酒精性脂肪性肝炎（NASH）大鼠内毒素及其受体的影响。
将56只SD大鼠分为7组。所有动物均给予高脂饮食12周。从第5周起，对非酒精性脂肪性肝炎（NASH）大鼠分别给予低剂量、中剂量、高剂量中药及立普妥进行治疗。在第12周结束时处死所有大鼠。在光学显微镜下观察肝脏病理变化。测定血清脂质、丙氨酸氨基转移酶（ALT）、内毒素（ET）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平。采用免疫组织化学法观察CD14和核转录因子κB（NF-κB）的表达。采用逆转录聚合酶链反应（RT-PCR）检测脂多糖结合蛋白（LBP）、Toll样受体4（TLR-4）、髓样分化蛋白2（MD-2）和诱导型一氧化氮合酶（iNOS）mRNA的表达。
第12周时，中剂量组血清内毒素水平（0.0225±0.0112 EU/l）低于高脂饮食模型组（0.2249±0.098 EU/l），差异有统计学意义（P<0.01）。中剂量组血清TNF-α和IL-1β水平的平均值（1.604±0.302 ng/ml和0.052±0.024 ng/ml）与高脂饮食模型组（4.029±1.180 ng/ml和14.944±0.491 ng/ml；P<0.01和P<0.01）相比显著降低。中剂量组CD?14和NF-κB的表达较高脂饮食模型组降低。中剂量组LBP mRNA（0.284±0.105）和TLR-4 mRNA（0.290±0.123）的表达较高脂饮食模型组（1.060±0.158和1.261±0.368；P<0.01和P<0.01）下调。中剂量组MD-2和iNOS基因表达分别为0.?132±0.058和0.164±0.061，与高脂饮食模型组（0.795±0.294和1.?029±0.388；P<0.01和P<0.01）相比显著降低。
非酒精性脂肪性肝炎（NASH）的发病机制可能与血清内毒素水平升高、肝组织内毒素受体上调及肝脏炎症损伤增强有关。中药是治疗非酒精性脂肪性肝炎（NASH）的有效药物。它可通过减轻脂多糖诱导肝损伤产生显著疗效。
