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Objective:To investigate the regulation and mechanism of chronic Trichinella spiralis ( Ts) infection on liver immunopathology in mice co-infected with Plasmodium berghei ANKA( PbA). Methods:According to body weight, 64 specific pathogen free female Kunming mice (6 - 8 weeks old, weighting 22 - 25 g) were divided into 4 groups by using random number table method. Control group: uninfected; Ts group: mice were mono-infected with 30 Ts larvae by oral gavage on day 0; PbA group: mice were mono-infected with 1 × 10 6PbA-infected red blood cells in 0.1 ml of phosphate buffer (PBS) administered by intraperitoneal injection on day 121; co-infected ( Ts+PbA) group: mice were infected with 30 Ts larvae by oral gavage and intraperitoneal injected with 1 × 10 6PbA-infected red blood cells in 0.1 ml PBS on day 121 after Ts infection. There were 16 mice in each group, in which 10 mice in each group were monitored for the survival rate. The peripheral red blood cell parasitemia of PbA group and Ts + PbA group were monitored every other day by light microscope examination of Giemsa-stained thin tail-blood smears from day 3 after PbA infection. Mice were sacrificed at day 135 after Ts infection and/or at day 15 after PbA infection, the mouse body weight and liver weight were measured, and the liver index were calculated. Ts-infected mice were monitored by a light microscope examination of diaphragm compression slide. Under a light microscope, the liver pathology and liver fibrosis of mice were observed and compared with hematoxylin-eosin (HE) staining and Sirius red staining, respectively. The F4/80 + Kupffer cells in liver of mice were examined by immunohistochemical staining. Results:After infection with Ts or PbA, Ts larvae cysts were observed in diaphragm tissues and PbA were observed in red blood cells under the light microscope. After PbA infection, there was no significant difference in survival rate between PbA group and Ts+ PbA group ( P > 0.05). Compared with PbA group, the peripheral red blood cell parasitemia was significantly decreased in Ts+ PbA group on days 11 and 15 after PbA infection (%: 27.104 ± 7.623 vs 45.032 ± 9.849, 60.218 ± 2.776 vs 76.778 ± 6.351, P < 0.05), and the liver index and the liver pathology score were significantly decreased in Ts+ PbA group ( P < 0.05). Sirius red staining showed that the positive area of liver fibrosis in Ts+ PbA group was significantly higher than that in PbA group ( P < 0.05). Immunohistochemical staining showed that the average optical density value of F4/80 + Kupffer cells in Ts+ PbA group was significantly higher than that in PbA group ( P < 0.01). Conclusion:Chronic Ts infection may reduce the peripheral red blood cell parasitemia, increase F4/80 + Kupffer cells expression in liver, and attenuate liver pathology in mice co-infected with PbA.
ABSTRACT
Parasitic diseases still remain the world's greatest health problems and cause huge economic burden in poor areas. The drugs currently used to treat protozoiases and helminthiases have certain defects, and it is urgent to develop more effective therapeutic drugs for these diseases. Berberine is one kind of important anti-inflammatory agents originally derived from Coptis rhizoma. The derivatives of berberine are obtained by modifying the structural site of berberine. In addition to its anti-inflammatory and anti-microbial activities, berberine and its derivatives also have significant anti-parasitic activity. In this paper, we summarized recent progress in the use of berberine and its derivatives against the infections of protozoa ( Leishmania spp ., Trypanosoma spp. , Toxoplasma gondii, Plasmodium falciparum, and Eimeria tenella) and helminths ( Schistosoma mansoni, Schistosoma. japonicum, Echinococcus granulosus, and Toxocara canis), which may providea useful reference for researchers in this field.
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Objective To evaluate the role of spinal phosphatidyl-inositol 3-kinase/Akt (PI3k/Akt) signaling pathway in the maintenance of bone cancer pain (BCP) in rats and its relationship with microglial activation.Methods Forty healthy female Sprague-Dawley rats,weighing 180-200 g,were randomly divided into 5 groups (n =8 each):sham operation group (group S) ; PI3K inhibitor LY294002 group (group L) ; group BCP; BCP + dimethyl sulfoxide (DMSO) group (group BCP + D) ; BCP + LY294002 group (group BCP + L).BCP was induced by inoculating Walker 256 mammary gland carcinoma cells into the medullary cavity of the left tibia.At 7-9 days after inoculation,LY294002 2.5 μg/10 μl was injected intrathecally in L and BCP + L groups,normal saline 10 μl was injected intrathecally in S and BCP groups,and 5％ DMSO 10 μl was injected intrathecally in BCP+ D group once a day.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before inoculation and 1,3,5,7,8 and 9 days after inoculation.The rats were sacrificed after MWT was measured on day 9 after inoculation and the L4-6 segments of the spinal cord were removed to determinate the activation of spinal microglia using immunofluorescence.Results Compared with group S,MWT was significantly decreased,and the activation of spinal microglia was increased in BCP,BCP + D and BCP+ L groups.Compared with BCP and BCP + D groups,MWT was significantly increased,and the activation of spinal microglia was decreased in BCP + D group.Conclusion Spinal PI3K/Akt signaling pathway is involved in the maintenance of BCP possibly through activating microglia in spinal dorsal horns of rats.