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目的观察木瓜提取物对高脂饮食联合腹腔注射猪血清致脂肪性肝纤维化的预防保护作用,并初步探讨其作用机制。方法取雌雄各半BABL/C小鼠48只,随机分成4组,每组12只,即正常对照组,模型组,木瓜提取物低(100 mg·kg-1)、高剂量组(300 mg·kg-1)。除正常对照组给予普通饲料外,其余各组均给予高脂饲料造模,同时木瓜提取物低、高剂量组分别给予100,300 mg·kg-1的木瓜提取物灌胃,持续10周;除正常对照组小鼠外,其余各组小鼠在第5周腹腔注射猪血清,持续3周。观察并记录上述各组小鼠造模前后体质量变化、行为和形态变化。苏木精-伊红(HE)、Masson染色,光镜下观察肝组织炎症及肝纤维化情况;用RT-PCR法检测RNA依赖的蛋白激酶样内质网激酶(PERK),肌醇需求酶1(IRE-1),转录因子6(ATF6),真核起始转录因子2α亚单位(e IF2α),组织型金属蛋白酶-1(TIMP-1),α-平滑肌肌动蛋白(α-SMA),胶原蛋白1型(COL 1A1);用Western Blot法检测葡萄糖调节蛋白78(GRP78),肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β),胶原蛋白1型(COL 1A1)。结果通过肝脏外观、HE和Masson染色后观察,与模型组比较,木瓜提取物低、高剂量组的小鼠肝脏损伤和纤维化程度明显改善,肝组织的PERK、IRE-1、ATF6、e IF2α、TIMP-1、α-SMA、COL 1A1的m RNA表达显著降低(P<0.05),GRP78、TNF-α、IL-1β、COL 1A1的蛋白表达显著降低(P<0.05)。结论木瓜提取物对脂肪性肝纤维化有较好的预防保护作用,其机制可能与对抗内质网应激(ERS)偶联炎症反应有关。
Objective To observe the preventive and protective effects of papaya extract on fatty liver fibrosis induced by high fat diet combined with intraperitoneal injection of swine serum and to explore its mechanism. Methods 48 male and female BABL / C mice were randomly divided into 4 groups with 12 mice in each group. The mice in the model group, papaya extract low (100 mg · kg -1) and high dose group (300 mg) Kg-1). In addition to the normal control group given ordinary feed, the other groups were given high-fat diet modeling, while papaya extract low and high dose group were given 100,300 mg · kg-1 papaya extract gavage for 10 weeks; except normal Control mice, the remaining mice in each group were injected intraperitoneally with pig serum for 5 weeks. Observe and record the above groups of mice before and after modeling the changes in body mass, behavior and morphological changes. Hematoxylin-eosin (HE) and Masson staining were used to observe the liver inflammation and hepatic fibrosis under light microscope. RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE-1), transcription factor 6 (ATF6), e IF2α, TIMP-1, α-smooth muscle actin ), Collagen type 1 (COL 1A1); Western blot was used to detect the expression of GRP78, TNF-α, IL-1β, (COL 1A1). Results The liver appearance, HE and Masson staining were observed. Compared with the model group, the liver damage and fibrosis of mice in the low and high dose groups of papaya extract were significantly improved. The expression of PERK, IRE-1, ATF6 and e IF2α (P <0.05). The mRNA expression of GRP78, TNF-α, IL-1β and COL 1A1 in TIMP-1, α-SMA and COL 1A1 were significantly decreased (P <0.05). Conclusion Papaya extract has a good preventive and protective effect on fatty liver fibrosis, and its mechanism may be related to the inflammatory reaction of endoplasmic reticulum stress (ERS).