Objective： To observe the effect of Gengnianchun Recipe （更年春方, GNC） on bone mineral density （BMD）, bone biomechanical parameters and serum lipid level in the bilaterally ovariectomized （OVX） rats and to exp...Objective： To observe the effect of Gengnianchun Recipe （更年春方, GNC） on bone mineral density （BMD）, bone biomechanical parameters and serum lipid level in the bilaterally ovariectomized （OVX） rats and to explore the prophylactic and therapeutic action of GNC on ovariectomy induced osteoporosis and hyperlipidemia. Methods： OVX SD rats, 10- 12 months old, were divided into different groups and fed with GNC 2 g/d, GNC 1 g/d and Nilestriol 0. 125 mg/week, respectively for 4 months to observe the change of BMD and bone biomechanical parameters of the lumbar vertebrae, and the serum levels of total cholesterol （TO）, triglyceride（TG）, high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）, and to compare the effect of the two drugs on the morphology of the uterus. Results： There was marked reduction in BMD and biomechanical parameters in lumbar vertebrae （ P〈0. 01 ） and increase of serum TO and LDL-C levels （ P〈0. 01 ） in rats after OVX. GNC or Nilestriol significantly improved the decreased BMD and biomechanical parameters of the lumbar vertebrae （ P〈0.05 or P〈0. 01 ）, and reduced the serum TO and LDL-C levels （ P〈0. 01 ）. In the Nilestriol group, the wet weight of uterus got increased obviously （ P〈0.01 ）, the number of uterine glands increased, uterine columnar epithelium thickened, and the mitotic figures in the epithelial stroma and myointimal cells augmented. But no such effect in wet weight and morphology of uterus was found in the GNC group. Conclusion： GNC could increase the BMD and biomechanical parameters of the lumbar vertebrae, reduce the serum TO and LDL-C levels, yet produce no adverse reaction in stimulating proliferation and hypertrophy of uterus.展开更多
AIM： To investigate the location alteration of Smad2 and Smad4 mRNAs in the liver during and after fibrogenesis in rats. METHODS： Eighty male Wistar rats weighing approximately 200 g each were used. The rat models o...AIM： To investigate the location alteration of Smad2 and Smad4 mRNAs in the liver during and after fibrogenesis in rats. METHODS： Eighty male Wistar rats weighing approximately 200 g each were used. The rat models of experimental hepatic fibrosis were established by injection with carbon tetrachloride （CCh）, normal rats and rats were injected with olive oil and served as control groups. In situ hybridization（ISH） was used to detect the Smad2 and Smad4 mRNA in liver. RESULTS： In situ hybridization showed Smad2 and Smad4 mRNA expressions in the cytoplasm of hepatic stellate cells （HSC）, fibroblasts and myofibroblasts around the central vein and hepatic sinus during and after fibrogenesis. Expression of Smad2, 4 mRNA was higher than that in normal and control rats. CONCLUSION： In the process of and after hepatic fibrosis formation, HSC, fibroblasts and myofibroblasts are the major cells that express Smad2 and Smad4. The more serious the hepatic fibrosis is in the injured liver, the higher the level of Smad2 and Smad4 gene expression is during and after fibrogenesis respectively.展开更多
This study was conducted to investigate the effect of Shenning II decoction on renal function, renal pathology, epithelial-to-mesenchymal transition (EMT), and Wnt/beta-catenin signaling in unilateral ureteral obstruc...This study was conducted to investigate the effect of Shenning II decoction on renal function, renal pathology, epithelial-to-mesenchymal transition (EMT), and Wnt/beta-catenin signaling in unilateral ureteral obstruction (UUO) renal fibrosis. Sprague-Dawley rats were randomly divided into blank control, sham-operated, UUO model (untreated), and UUO with Shenning decoction treatment (high, medium, and low dose) groups. Renal function was evaluated based on blood urea nitrogen (BUN) and serum creatinine (Scr) levels. Histopathological analysis of rat kidney tubular tissue was carried out and E-cadherin, fibronectin, vimentin, Wnt4, glycogen synthase kinase (GSK)<i>β</i>, low-density lipoprotein receptor-related protein (LRP)5, LRP6, <i>β</i>-catenin, Snail, and fibroblast-specific protein (FSP)1 expression was evaluated by immunohistochemistry, western blotting, and real-time PCR. BUN and Scr were found to be increased in UUO when compared with the sham rats (P < 0.05), but this was reversed (albeit non-significantly) in rats treated with high and medium doses of Shenning II (P > 0.05). Shenning II decoction decreased histopathological scores relative to the UUO rats (P < 0.05). Protein expression of E-cadherin was increased, whereas that of vimentin, Wnt4, <i>β</i>-catenin, and fibronectin was decreased in Shenning I-treated rats, when compared with the untreated UUO rats, as determined by immunohistochemistry and western blotting (P < 0.05). Wnt4, <i>β</i>-catenin, GSK-3<i>β</i>, LRP5, LRP6, Snail, and FSP1 mRNA levels were also downregulated by Shenning II decoction treatment (P < 0.05). Shenning II decoction, therefore, protects against renal fibrosis by blocking renal tubular EMT via suppression of Wnt/beta-catenin signaling.展开更多
OBJECTIVE:To investigate the effectiveness of Banxia Xiexin decoction(BXD)in a rat model of chronic atrophic gastritis(CAG).METHODS:Sixty 6-week-old healthy Wistar rats(30 males,30 females)were used in the present stu...OBJECTIVE:To investigate the effectiveness of Banxia Xiexin decoction(BXD)in a rat model of chronic atrophic gastritis(CAG).METHODS:Sixty 6-week-old healthy Wistar rats(30 males,30 females)were used in the present study.A rat model of CAG was successfully established using the combined active immunization/ethanol/sodium deoxycholate method.BXD was prepared from a mixture of seven Chinese herbs,and was intragastrically administered to CAG rats at three different doses(6,12,and 24 g·kg^-1·d^-1).Af-ter 24 weeks,the rats were euthanized,and gastric tissue specimens were collected.Gastric mucosal specimens were stained with hematoxylin and eosin for histological examination to evaluate the degree of inflammation and morphological changes.Immunohistochemical staining was performed to examine the mucosal expression of proliferating cell nuclear antigen.Serum gastrin levels were measured using radioimmunoassay.The expression of Notch signaling-associated genes was examined by quantitative polymerase chain reaction and Western blot assay.RESULTS:BXD at all three doses significantly reversed the adverse effects generated by CAG in rats.Compared with control rats,the CAG rats who were administered BXD had an accelerated growth rate,reduced inflammatory cell infiltration,improved gastric mucosal morphology,augmented thickness of the gastric mucosa,increased number of gastric glands,enhanced mucosal expression of proliferating cell nuclear antigen,and elevated serum gastrin levels.展开更多
Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity.Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbαcan inhibit thrombosis without affecting phy...Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity.Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbαcan inhibit thrombosis without affecting physiological coagulation.Mac-1-GPIbαis proposed as a potential safety target for antithrombotic agents.Guanxinning tablet(GXNT)is an oral Chinese patent medicine used for the treatment of angina pectoris,which contains phenolic acid active ingredients,such as salvianolic acids,ferulic acid,chlorogenic acid,caffeic acid,rosmarinic acid,tanshinol,and protocatechualdehyde.Our previous studies demonstrated that GXN exhibited significant antithrombotic effects,and clinical studies suggested that it did not increase bleeding risk.In addition,GXN exerted a significantly regulatory effect on immune inflammation.In the current study,we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction.First,we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred,but also had a certain promoting effect on the healing of gastric ulcer.Second,in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate(PMA),the adhesion and aggregation of leukocytes with human platelets were reduced.It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes,and inhibited platelet activation due to leukocyte engagement via Mac-1.Overall,the results suggest that GXN may be a safe antithrombotic agent,and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.展开更多
文摘Objective： To observe the effect of Gengnianchun Recipe （更年春方, GNC） on bone mineral density （BMD）, bone biomechanical parameters and serum lipid level in the bilaterally ovariectomized （OVX） rats and to explore the prophylactic and therapeutic action of GNC on ovariectomy induced osteoporosis and hyperlipidemia. Methods： OVX SD rats, 10- 12 months old, were divided into different groups and fed with GNC 2 g/d, GNC 1 g/d and Nilestriol 0. 125 mg/week, respectively for 4 months to observe the change of BMD and bone biomechanical parameters of the lumbar vertebrae, and the serum levels of total cholesterol （TO）, triglyceride（TG）, high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）, and to compare the effect of the two drugs on the morphology of the uterus. Results： There was marked reduction in BMD and biomechanical parameters in lumbar vertebrae （ P〈0. 01 ） and increase of serum TO and LDL-C levels （ P〈0. 01 ） in rats after OVX. GNC or Nilestriol significantly improved the decreased BMD and biomechanical parameters of the lumbar vertebrae （ P〈0.05 or P〈0. 01 ）, and reduced the serum TO and LDL-C levels （ P〈0. 01 ）. In the Nilestriol group, the wet weight of uterus got increased obviously （ P〈0.01 ）, the number of uterine glands increased, uterine columnar epithelium thickened, and the mitotic figures in the epithelial stroma and myointimal cells augmented. But no such effect in wet weight and morphology of uterus was found in the GNC group. Conclusion： GNC could increase the BMD and biomechanical parameters of the lumbar vertebrae, reduce the serum TO and LDL-C levels, yet produce no adverse reaction in stimulating proliferation and hypertrophy of uterus.
基金Supported by the Research Foundation of Department of Education of Heilongjiang Province, No.10551131
文摘AIM： To investigate the location alteration of Smad2 and Smad4 mRNAs in the liver during and after fibrogenesis in rats. METHODS： Eighty male Wistar rats weighing approximately 200 g each were used. The rat models of experimental hepatic fibrosis were established by injection with carbon tetrachloride （CCh）, normal rats and rats were injected with olive oil and served as control groups. In situ hybridization（ISH） was used to detect the Smad2 and Smad4 mRNA in liver. RESULTS： In situ hybridization showed Smad2 and Smad4 mRNA expressions in the cytoplasm of hepatic stellate cells （HSC）, fibroblasts and myofibroblasts around the central vein and hepatic sinus during and after fibrogenesis. Expression of Smad2, 4 mRNA was higher than that in normal and control rats. CONCLUSION： In the process of and after hepatic fibrosis formation, HSC, fibroblasts and myofibroblasts are the major cells that express Smad2 and Smad4. The more serious the hepatic fibrosis is in the injured liver, the higher the level of Smad2 and Smad4 gene expression is during and after fibrogenesis respectively.
文摘This study was conducted to investigate the effect of Shenning II decoction on renal function, renal pathology, epithelial-to-mesenchymal transition (EMT), and Wnt/beta-catenin signaling in unilateral ureteral obstruction (UUO) renal fibrosis. Sprague-Dawley rats were randomly divided into blank control, sham-operated, UUO model (untreated), and UUO with Shenning decoction treatment (high, medium, and low dose) groups. Renal function was evaluated based on blood urea nitrogen (BUN) and serum creatinine (Scr) levels. Histopathological analysis of rat kidney tubular tissue was carried out and E-cadherin, fibronectin, vimentin, Wnt4, glycogen synthase kinase (GSK)<i>β</i>, low-density lipoprotein receptor-related protein (LRP)5, LRP6, <i>β</i>-catenin, Snail, and fibroblast-specific protein (FSP)1 expression was evaluated by immunohistochemistry, western blotting, and real-time PCR. BUN and Scr were found to be increased in UUO when compared with the sham rats (P < 0.05), but this was reversed (albeit non-significantly) in rats treated with high and medium doses of Shenning II (P > 0.05). Shenning II decoction decreased histopathological scores relative to the UUO rats (P < 0.05). Protein expression of E-cadherin was increased, whereas that of vimentin, Wnt4, <i>β</i>-catenin, and fibronectin was decreased in Shenning I-treated rats, when compared with the untreated UUO rats, as determined by immunohistochemistry and western blotting (P < 0.05). Wnt4, <i>β</i>-catenin, GSK-3<i>β</i>, LRP5, LRP6, Snail, and FSP1 mRNA levels were also downregulated by Shenning II decoction treatment (P < 0.05). Shenning II decoction, therefore, protects against renal fibrosis by blocking renal tubular EMT via suppression of Wnt/beta-catenin signaling.
基金Supported by the Natural Science Foundation of Zhejiang Province(Notch signaling-based Mechanistic Studies on the Therapeutic Role of Banxia Xiexin Decoction in Chronic Atrophic Gastritis,No.LY15H270013)
文摘OBJECTIVE:To investigate the effectiveness of Banxia Xiexin decoction(BXD)in a rat model of chronic atrophic gastritis(CAG).METHODS:Sixty 6-week-old healthy Wistar rats(30 males,30 females)were used in the present study.A rat model of CAG was successfully established using the combined active immunization/ethanol/sodium deoxycholate method.BXD was prepared from a mixture of seven Chinese herbs,and was intragastrically administered to CAG rats at three different doses(6,12,and 24 g·kg^-1·d^-1).Af-ter 24 weeks,the rats were euthanized,and gastric tissue specimens were collected.Gastric mucosal specimens were stained with hematoxylin and eosin for histological examination to evaluate the degree of inflammation and morphological changes.Immunohistochemical staining was performed to examine the mucosal expression of proliferating cell nuclear antigen.Serum gastrin levels were measured using radioimmunoassay.The expression of Notch signaling-associated genes was examined by quantitative polymerase chain reaction and Western blot assay.RESULTS:BXD at all three doses significantly reversed the adverse effects generated by CAG in rats.Compared with control rats,the CAG rats who were administered BXD had an accelerated growth rate,reduced inflammatory cell infiltration,improved gastric mucosal morphology,augmented thickness of the gastric mucosa,increased number of gastric glands,enhanced mucosal expression of proliferating cell nuclear antigen,and elevated serum gastrin levels.
文摘Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity.Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbαcan inhibit thrombosis without affecting physiological coagulation.Mac-1-GPIbαis proposed as a potential safety target for antithrombotic agents.Guanxinning tablet(GXNT)is an oral Chinese patent medicine used for the treatment of angina pectoris,which contains phenolic acid active ingredients,such as salvianolic acids,ferulic acid,chlorogenic acid,caffeic acid,rosmarinic acid,tanshinol,and protocatechualdehyde.Our previous studies demonstrated that GXN exhibited significant antithrombotic effects,and clinical studies suggested that it did not increase bleeding risk.In addition,GXN exerted a significantly regulatory effect on immune inflammation.In the current study,we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction.First,we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred,but also had a certain promoting effect on the healing of gastric ulcer.Second,in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate(PMA),the adhesion and aggregation of leukocytes with human platelets were reduced.It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes,and inhibited platelet activation due to leukocyte engagement via Mac-1.Overall,the results suggest that GXN may be a safe antithrombotic agent,and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.
