Protective Effect of Zengye Decoction(增液汤)on Submandibular Glands in Nonobese Diabetic Mice
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摘要
Objective: To investigate the protective effect of Zengye Decoction(增液汤, ZYD) on the submandibular glands(SMGs) in nonobese diabetic(NOD) mice. Methods: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine(HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon(IFN-γ), interleukin-10(IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide(VIP) in the submandibular glands were measured by realtime polymerase chain reaction. Results: Compared with the model group, the salivary flow of the ZYD group significantly increased(P<0.05), the extent of the histological changes was ameliorated(P<0.05), and the Th1/Th2 cytokine imbalance was remedied(P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated(P<0.05). Conclusions: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.
Objective: To investigate the protective effect of Zengye Decoction(增液汤, ZYD) on the submandibular glands(SMGs) in nonobese diabetic(NOD) mice. Methods: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine(HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon(IFN-γ), interleukin-10(IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide(VIP) in the submandibular glands were measured by realtime polymerase chain reaction. Results: Compared with the model group, the salivary flow of the ZYD group significantly increased(P<0.05), the extent of the histological changes was ameliorated(P<0.05), and the Th1/Th2 cytokine imbalance was remedied(P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated(P<0.05). Conclusions: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.
Objective: To investigate the protective effect of Zengye Decoction(增液汤, ZYD) on the submandibular glands(SMGs) in nonobese diabetic(NOD) mice. Methods: Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine(HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon(IFN-γ), interleukin-10(IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide(VIP) in the submandibular glands were measured by realtime polymerase chain reaction. Results: Compared with the model group, the salivary flow of the ZYD group significantly increased(P<0.05), the extent of the histological changes was ameliorated(P<0.05), and the Th1/Th2 cytokine imbalance was remedied(P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated(P<0.05). Conclusions: ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.
引文
1.Zhao JS,Tong WD.Pathophysiology of slow transit constipation.Chin J Gastrointest Surg(Chin)2012;15:758-760.
2.Cheng J.Theoretical and experimental research on the point of the correlation between lung and large intestine in fluids metabolism[dissertation].Wuhan:Hubei University of Chinese Medicine;2010.
3.Hauk V,Calafat M,Larocca L,Fraccaroli L,Grasso E,Ramhorst R,et al.Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sj?gren's syndrome.Clin Exp Immunol 2011;166:309-316.
4.Lodde BM,Mineshiba F,Wang J,Cotrim AP,Afione S,Tak PP,et al.Effect of human vasoactive intestinal peptide gene transfer in a murine model of Sj?gren's syndrome.Ann Rheum Dis 2006;65:195-200.
5.Sun LY,Ma YX,Li WW,Wu XD,Xiao HB,Hu XY,et al.The effect of Zengye Decoction on Th1 cytokines in Sj?gren's syndrome model mice.Acta Chin Med Pharmacol(Chin)2010;38(6):42-44.
6.Sasaki K,Duan J,Murohara T,Ikeda H,Shintani S,Shimada T,et al.Rescue of hypercholesterolemia-related impairment of angiogenesis by oral folate supplementation.J Am Coll Cardiol 2003;42:364-372.
7.Bojunga J,Kusterer K,Bacher M,Kurek R,Usadel KH,Renneberg H.Macrophage migration inhibitory factor and development of type-1 diabetes in non-obese diabetic mice.Cytokine 2003;21:179-186.
8.Chisholm DM,Mason DK.Labial salivary gland biopsy in Sj?gren's disease.J Clin Pathol 1968;21:656-660.
9.Kok MR,Yamano S,Lodde BM,Wang J,Couwenhoven RI,Yakar S,et al.Local adeno-associated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of Sj?gren's syndrome.Hum Gene Ther2003;14:1605-1618.
10.Thomas PB,Samant DM,Selvam S,Wei RH,Wang Y,Stevenson D,et al.Adeno-associated virus-mediated IL-10gene transfer suppresses lacrimal gland immunopathology in a rabbit model of autoimmune dacryoadenitis.Invest Ophthalmol Vis Sci 2010;51:5137-5144.
11.Brennan MT,Fox PC.Cytokine mRNA expression in the labial salivary glands of healthy volunteers.Oral Dis2000;6:222-226.
12.Kohriyama K,Katayama Y.Disproportion of helper Tcell subsets in peripheral blood of patients with primary Sj?gren's syndrome.Autoimmunity 2000;32:67-72.
13.Fox RI,Kang HI,Ando D,Abrams J,Pisa E.Cytokine mRNA expression in salivary gland biopsies of Sj?gren's syndrome.J Immunol 1994;152:5532-5539.
14.van Woerkom JM,Kruize AA,Wenting-Van WM,Knol E,Bihari IC,Jacobs J W,et al.Salivary gland and peripheral blood T helper 1 and 2 cell activity in Sj?gren's syndrome compared with non-Sjogren's sicca syndrome.Ann Rheum Dis 2005;64:1474-1479.
15.Wu G L,Li TY,Fan YS,Yu GY,Chen J.Effect of Chinese herbal medicine for nourishing yin,supplementing qi,and activating blood on the Th1/Th2 immune balance in peripheral blood in patients with primary Sj?gren's syndrome.Chin J Integr Med 2013;19:696-700.
16.Szema AM,Hamidi SA,Golightly MG,Rueb TP,Chen JJ.VIP regulates the development and proliferation of treg in vivo in spleen.Allergy Asthma Clin Immunol 2011;7:19.
17.Luo Q,Wang Y,Feng D,Xu Y,Xu L.Vasoactive intestinal peptide attenuates concanavalin A-mediated liver injury.Eur J Pharmacol 2009;607:226-233.
18.Larocca L,Calafat M,Roca V,Franchi A M,Leiros C P.VIPlimits LPS-induced nitric oxide production through IL-10 in NODmice macrophages.Int Immunopharmacol 2007;7:1343-1349.
2.Cheng J.Theoretical and experimental research on the point of the correlation between lung and large intestine in fluids metabolism[dissertation].Wuhan:Hubei University of Chinese Medicine;2010.
3.Hauk V,Calafat M,Larocca L,Fraccaroli L,Grasso E,Ramhorst R,et al.Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sj?gren's syndrome.Clin Exp Immunol 2011;166:309-316.
4.Lodde BM,Mineshiba F,Wang J,Cotrim AP,Afione S,Tak PP,et al.Effect of human vasoactive intestinal peptide gene transfer in a murine model of Sj?gren's syndrome.Ann Rheum Dis 2006;65:195-200.
5.Sun LY,Ma YX,Li WW,Wu XD,Xiao HB,Hu XY,et al.The effect of Zengye Decoction on Th1 cytokines in Sj?gren's syndrome model mice.Acta Chin Med Pharmacol(Chin)2010;38(6):42-44.
6.Sasaki K,Duan J,Murohara T,Ikeda H,Shintani S,Shimada T,et al.Rescue of hypercholesterolemia-related impairment of angiogenesis by oral folate supplementation.J Am Coll Cardiol 2003;42:364-372.
7.Bojunga J,Kusterer K,Bacher M,Kurek R,Usadel KH,Renneberg H.Macrophage migration inhibitory factor and development of type-1 diabetes in non-obese diabetic mice.Cytokine 2003;21:179-186.
8.Chisholm DM,Mason DK.Labial salivary gland biopsy in Sj?gren's disease.J Clin Pathol 1968;21:656-660.
9.Kok MR,Yamano S,Lodde BM,Wang J,Couwenhoven RI,Yakar S,et al.Local adeno-associated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of Sj?gren's syndrome.Hum Gene Ther2003;14:1605-1618.
10.Thomas PB,Samant DM,Selvam S,Wei RH,Wang Y,Stevenson D,et al.Adeno-associated virus-mediated IL-10gene transfer suppresses lacrimal gland immunopathology in a rabbit model of autoimmune dacryoadenitis.Invest Ophthalmol Vis Sci 2010;51:5137-5144.
11.Brennan MT,Fox PC.Cytokine mRNA expression in the labial salivary glands of healthy volunteers.Oral Dis2000;6:222-226.
12.Kohriyama K,Katayama Y.Disproportion of helper Tcell subsets in peripheral blood of patients with primary Sj?gren's syndrome.Autoimmunity 2000;32:67-72.
13.Fox RI,Kang HI,Ando D,Abrams J,Pisa E.Cytokine mRNA expression in salivary gland biopsies of Sj?gren's syndrome.J Immunol 1994;152:5532-5539.
14.van Woerkom JM,Kruize AA,Wenting-Van WM,Knol E,Bihari IC,Jacobs J W,et al.Salivary gland and peripheral blood T helper 1 and 2 cell activity in Sj?gren's syndrome compared with non-Sjogren's sicca syndrome.Ann Rheum Dis 2005;64:1474-1479.
15.Wu G L,Li TY,Fan YS,Yu GY,Chen J.Effect of Chinese herbal medicine for nourishing yin,supplementing qi,and activating blood on the Th1/Th2 immune balance in peripheral blood in patients with primary Sj?gren's syndrome.Chin J Integr Med 2013;19:696-700.
16.Szema AM,Hamidi SA,Golightly MG,Rueb TP,Chen JJ.VIP regulates the development and proliferation of treg in vivo in spleen.Allergy Asthma Clin Immunol 2011;7:19.
17.Luo Q,Wang Y,Feng D,Xu Y,Xu L.Vasoactive intestinal peptide attenuates concanavalin A-mediated liver injury.Eur J Pharmacol 2009;607:226-233.
18.Larocca L,Calafat M,Roca V,Franchi A M,Leiros C P.VIPlimits LPS-induced nitric oxide production through IL-10 in NODmice macrophages.Int Immunopharmacol 2007;7:1343-1349.
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