Role of succinate dehydrogenase deficiency and oncometabolites in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.At the molecular level,GISTs can be categorized into two groups based on the causative oncogenic mutations.Approximately 85%of GISTs are caused by gain-of-function mutations in the tyrosine kinase receptor KIT or platelet-derived growth factor receptor alpha(PDGFRA).The remaining GISTs,referred to as wild-type(WT)GISTs,are often deficient in succinate dehydrogenase complex(SDH),a key metabolic enzyme complex in the tricarboxylic acid(TCA)cycle and electron transport chain.SDH deficiency leads to the accumulation of succinate,a metabolite produced by the TCA cycle.Succinate inhibitsα-ketoglutarate-dependent dioxygenase family enzymes,which comprise approximately 60 members and regulate key aspects of tumorigenesis such as DNA and histone demethylation,hypoxia responses,and m6A mRNA modification.For this reason,succinate and metabolites with similar structures,such as D-2-hydroxyglutarate and fumarate,are considered oncometabolites.In this article,we review recent advances in the understanding of how metabolic enzyme mutations and oncometabolites drive human cancer with an emphasis on SDH mutations and succinate in WT GISTs.

A NOVEL Ser73Gly VARIATION OF SUCCINATE DEHYDROGENASE,SUBUNIT D AND A Cys634Gly MUTATION IN Ret PROTO-ONCOGENE OBSERVED IN A CHINESE MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A PATIENT

Multiple endocrine neoplasia type 2A （ MEN2A ） is an autosomal dominant cancer syndrome that is characterized by medullary thyroid carcinoma （MTC）, pheochromaocytoma （50% - 60% of cases ）, and hyperplasia of the parathyroid glands （ 20% - 30% of cases ）. MEN-2A comprises a heterogeneous group of neoplastic disorders that most commonly have a single missense substitution of the Ret proto-oncogene （RET） involving exons 10 and 11. Here, we reported a novel case of MEN2A associated with two variations in two distinct genes, Cys634Gly in RET and a rare Ser73Gly substitution in succinate dehydrogenase, subunit D （SDHD）. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma but without parathyroid gland involvement, we speculated that this clinical feature could be correlated with the two substitutions. This is the first report of a MEN2A case involving two different changes one in the RET gene and the other in the SDHD gene.

Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell （HC） pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydregenase （SDH）, a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae. Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young （2-3 months） and aging （22-23 months） Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy. Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs. Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results sUggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.

Succinate dehydrogenase in Parkinson＇s disease

BACKGROUND： The prevalence of neurodegenerative disorders such as Parkinson＇s disease （PD） is increased by age. Alleviation of their symptoms and protection of normal neurons against degeneration are the main aspects of the researches to establish novel therapeutic strategies. Many studies have shown that mitochondria as the most important organelles in the brain which show impairment in PD models. Succinate dehydrogenase （SDH） as a component of the oxidative phosphorylation system in mitochondria connects Krebs cycle to the electron transport chain. Dysfunction or inhibition of the SDH can trigger mitochondrial impairment and disruption in ATP generation. Excessive in lipid synthesis and induction of the excitotoxicity as inducers in PD are controlled by SDH activity directly and indirectly. On the other hand, mutation in subunits of the SDH correlates with the onset of neurodegenerative disorders. Therefore, SDH could behave as one of the main regulators in neuroprotection. OBJECTIVE： In this review we will consider contribution of the SDH and its related mechanisms in PD. METHODS： Pubmed search engine was used to find published studies from 1977 to 2016. ＂Succinate dehydrogenase＂, ＂lipid and brain＂, ＂mitochondria and Parkinson＇s disease＂ were the main keywords for searching in the engine. RESULTS： Wide ranges of studies （59 articles） in neurodegenerative disorders especially Parkinson＇s disease like genetics of the Parkinson＇s disease, effects of the mutant SDH on cell activity and physiology and lipid alteration in neurodegenerative disorders have been used in this review. CONCLUSION： Mitochondria as key organelles in the energy generation plays crucial roles in PD. ETC complex in this organelle consists four complexes which alteration in their activities cause ROS generation and ATP depletion. Most of complexes are encoded by mtDNA while complex Ⅱ is the only part of the ETC which is encoded by nuclear genome. So, focusing on the SDH and related pathways which have important role in neuronal survival and SDH has a potential to further studies as a novel neuroproteetive agent.

Current research and treatment for gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.

Three-dimensional conformal intensity-modulated radiation therapy of left femur foci does not damage the sciatic nerve

During radiotherapy to kill femoral hydatid tapeworms, the sciatic nerve surrounding the focus can be easily damaged by the treatment. Thus, it is very important to evaluate the effects of ra- diotherapy on the surrounding nervous tissue. In the present study, we used three-dimensional, conformal, intensity-modulated radiation therapy to treat bilateral femoral hydatid disease in Meriones meridiani. The focus of the hydatid disease on the left femur was subiected to radio- therapy （40 Gy） for 14 days, and the right femur received sham irradiation. Hematoxylin-eosin staining, electron microscopy, and terminal deoxynucleotidyl transferase-dUTP nick end labeling assays on the left femurs showed that the left sciatic nerve cell structure was normal, with no ob- vious apoptosis after radiation. Trypan blue staining demonstrated that the overall protoscolex structure in bone parasitized with Echinococcus granulosus disappeared in the left femur of the animals after treatment. The mortality of the protoscolex was higher in the left side than in the right side. The succinate dehydrogenase activity in the protoscolex in bone parasitized with Echi- nococcus granulosus was lower in the left femur than in the right femur. These results suggest that three-dimensional conformal intensity-modulated radiation therapy achieves good therapeutic effects on the secondary bone in hydatid disease in Meriones meridiani without damaging the morphology or function of the sciatic nerve.

Hypoglycemic Activity of Jatrorrhizine

Summary： The hypoglycemic activity and its mechanism of Jatrorrhizine （Jat） were studied. The normal mice and alloxan-induced hyperglycemic mice were given with different doses of Jat. Blood glucose and liver glycogen levels were determined by spectrophotometry with glucose-oxidase and iodine reagents respectively. The levels of blood lactic acid （LC） and liver lactate dehydrogenase （LDH） activity were measured to explore the effect of Jat on anaerobic glycolysis. Succinate dehydrogenase （SDH） activity in liver was measured to evaluate the effect of Jat on aerobic glycolysis in liver. It was found that Jat （50 mg/kg, 100 mg/kg） could significantly decrease blood glucose level in a dose- and time-dependent manner in both normal and alloxan-diabetic mice, increase the activity of SDH, but had no significant effects on the LC level and LDH activity. Jat could significantly reduce the content of liver glycogen in normal mice. Moreover, Jat could inhibit the platelet aggregation in rabbits in vitro in a dose-effect relationship. It was concluded that Jat induced the pronounced decrease in blood glucose in normal and hyperglycemic mice. The hypoglycemic activity of Jat may be attributed to the enhancement of aerobic glycolysis.

AN EXPERIMENTAL STUDY OF ELECTROACUPUNCTURE ON AUDITORY IMPAIRMENT CAUSED BY KANAMYCIN IN GUINEA PIGS

Frequency following response(FFR)and auditory brain stem evoked potential response(ABR)were used to determine the auditory acuity in evaluating the effect of electro-acupuncture treatment of kanamycin-induced auditory impairment in guinea pigs.Thesuccinate dehydrogenase(SDH)activity and morphological changes of the inner earreceptors were examined under the light and scanning electron microscope in cochlearspread preparations.The results showed that 1)electro-acupuncture was effective but nosignificant differences were found among the stimulating wave forms;2)Tinggong(SI19),Yifeng(SJ 17),Shenshu(UB 23),Sanyinjiao(Sp 6),Zhubin(K 9)and Waiguan(SJ 5)are all effective acupoints,especially the combination of Tinggong(SI 19),Sanyinjiao(Sp6)and Zhubin(K 9)acupoints;3)improvement in the cochlear function and excitabilityof the cortical and lower auditory center and increase of the mitochondrial SDH activityand energy supply in hair cells might contribute to the mechanism of the treatment.

Attractin Gene Deficiency Contributes to Testis Vacuolization and Sperm Dysfunction in Male Mice

The effect of loss-of-function of Attractin （Atrn） on the male mouse reproduction system was examined in the study. The weights and pathological changes of testes and epididymes were compared between Atrn mutant （Atrnmg-3J） mice and wild-type mice （C3HeB/FeJ） at different months of age. The number and motility of sperms were measured in the mutant and control mice. Furthermore, the testicular lactate dehydrogenase （LDH） and succinate dehydrogenase （SDH） in these animals were detected. The fertility potential of the sperms was observed in vivo and in vitro. The results showed that the testes of 3-month-old Atrnmg-3J mice experienced no significantly different pathological changes from the control mice at the same month of age but the SDH activity was substantially reduced. In the 5-month-old mutant mice, as compared with the control mice, mild vacuolation was found in the testes, the density and motility of sperms were decreased in the epididymes, the sperm fertility was impaired and the testicular enzyme activity was reduced. It is concluded that the age-related Atrn gene progressively loses its function and can cause testis vacuolation and impaired sperm function, which may be responsible for the impairment of male reproductive ability.

Protection of melatonin against damage of sperm mitochondrial function induced by reactive oxygen species

Aim: To study the mitochondrial function damage of sperm induced by reactive oxygen species (ROS) and the protection of melatonin (MLT) against the damage. Methods: Normal function spermatozoa were selected from semen samples by Percoll gradient centrifugation technique. The ROS generated by the hypoxan-thine xanthine oxidase system was incubated with the normal spermatozoa in the presence or absence of MLT (6 mmol/L) for 30 and 60 minutes. After incubation, the activity of succinate dehydroge-nase (SDH) in the mitochondria of spermatozoa was assessed by histochemical method and spermatozoa were labeled with specific fluorescent probe of Rhodamine 123 to measure the mitochondrial membrane potential (MMP) by flow cytometry. Results: After the normal spermatozoa were incubated with ROS, The sperm MMP was significantly decreased and the SDH activity of almost decreased to zero. MLT reduced the mitochondrial damage induced by ROS. Conclusion: ROS damage the mitochondrial function of sperm by affecting sperm MMP and SDH activity of. MLT protects sperm mitochondria from the damage induced by ROS through its effective antioxidative potential.

An Enzymologic Study on Bone Marrow Cells in Patients with Aplastic Anemia Treated by Supplementing the Kidney and Removing Blood Stasis

The content of cytochrome oxidase (CCO), succinate dehydrogenase (SDH) and neutrophil alkaline phosphatase (NAP) in bone marrow cells in 68 cases of aplastic anemia before and after treatment was determined by computerized graphical analysis and compared with that of normal volunteers (control group). The significantly lowered CCO and SDH levels and the markedly increased NAP content before treatment (P<0.01) became approximately normal after that of supplementing the kidney and removing blood stasis (P >0.05).

Peripancreatic paraganglioma:Lesson from a round table

We described the case of a peripancreatic paraganglioma(PGL)misdiagnosed as pancreatic lesion.Surgical exploration revealed an unremarkable pancreas and a large well-defined cystic mass originating at the mesocolon root.Radical enucleation of the mass was performed,preserving the pancreatic tail.Histologically,a diagnosis of PGL was rendered.Interestingly,two previously unreported mutations,one affecting the KDR gene in exon 7 and another on the JAK3 gene in exon 4 were detected.Both mutations are known to be pathogenetic.Imaging and cytologic findings were blindly reviewed by an expert panel of clinicians,radiologists,and pathologists to identify possible causes of the misdiagnosis.The major issue was lack of evidence of a cleavage plane from the pancreas at imaging,which prompted radiologists to establish an intraparenchymal origin.The blinded revision shifted the diagnosis towards an extrapancreatic lesion,as the pancreatic parenchyma showed no structural alterations and no dislocation of the Wirsung duct.Ex post,the identified biases were the emergency setting of the radiologic examination and the very thin mesocolon sheet,which hindered clear definition of the lesion borders.Original endoscopic ultrasonography diagnosis was confirmed,emphasizing the intrinsic limit of this technique in detecting large masses.Finally,pathologic review favored a diagnosis of PGL due to the morphological features and immonohistochemical profile.Eighteen months after tumor excision,the patient is asymptomatic with no disease relapse evident by either radiology or laboratory tests.Our report strongly highlights the difficulties in rendering an accurate preoperative diagnosis of PGL.

The Ultracytochemical Effects of High Energy Shock Wave on Rabbit Liver

The ultracytochemical effects in the liver of rabbit undergoing high energy shock wave (HESW) were studied with electron microscope. The application of lanthanum as a tracer for ultrastructural study demonstrated that intracellular lanthanum could be observed, most of which entered the hepatocytes and its mitochondria. The lanthanum granules were also found to deposite in the zone of tight junctions of bile canaliculi, which indicated that the tight junctions had been damaged. The activities of succinate dehydrogenase (SDH) in liver cells, alkaline phosphatase (ALP) and thiamine pyrophosphatase (TPPase) on the wall of bile canaliculi became diminished obviously. Both the activites and localizations of TPPase had changed. Some TPPase from the damaged lysosome like vesicles and Golgi saccules of liver cells discharged into cytoplasm. TPPase reaction production in some bile canaliculi decreased. In the intercellular space of the liver cells and the tight junctions of bile canaliculi TPPase reaction could be seen. Ultrastructurally, the changes commonly seen were hydropic mitochondria and dilatation of rough endoplasmic reticulum. Serologic test demonstrated that there was an abnormal change of SGPT, SGOT and ALP. The results showed that HESW can damage the ultrastructure and function of liver.

The Effect of Ultra Low Concentrations of Some Biologically Active Substances on the Aerobic Respiration

For today it is known, that primary and secondary disorders of the aerobic respiration, which are based on mitochondrial deficiency, lead to a wide spectrum of clinical manifestations and diseases. Therefore, the question about effective correction of various types of energy exchange disorders remains topical. Thus, the aim of our work was the study effect of the complex of biologically active substances (BAS) in ultra low concentrations on the activity of key enzymes of aerobic energy metabolism succinate dehydrogenase (EC 1.3.99.1) (SQR) and mitochondrial glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) (GPD2). The human lymphocytes assays were tested in vitro (22 donors). In negative control lymphocytes, cell culture normal saline solution was added. Normal saline solution with NaN3 was added in positive control lymphocytes cell culture. Experimental cell culture contained NaN3 and BAS. Our investigations had been revealed increase SQR activity in the experimental cell culture as compared with positive control culture throughout the time of experiment (measurements were carried out at 4, 24, 48, 72 h of incubation). The SQR activity of experimental cell culture and negative control lymphocytes cell culture was equal up to 24 h of experiment. It showed neutralization of NaN3 inhibitory effect (during 24 h) due to BAS influence. Activity of base glycerophosphate shunt ferment GPD2 of experimental lymphocyte cell culture was not different from GPD2 index in the negative control, but was lower than GPD2 activity in the positive control. It also indicated neutralization NaN3 inhibitory effect due to BAS influence. So we had found that extremely low concentrations of selected BAS with their complex impact on human lymphocytes in vitro could effectively neutralize the inhibitory effect of NaN3 on processes of aerobic energy metabolism link.

Effect of IUD with Indomethacinon Rabbits Endometrium by Enzyme Histochemistry

The present paper reported the observation of the effect of IUD with indomethacin on enzyme activities of succinic dehydrogenase(SDH),nonspecific esterase(NSE)and ATPase in endomtrium of rabbits,and the comparison with copper intrauterine devices,silicon rubber and IUD with copper and indomethacin.The results indicated:1.In the group of indomethacin,the enzyme activities of SDH,NSE and ATPase were increased,while they were obviously decreased in IUD with copper.In the group of IUD with copper and indomethacin the enzyme activities also decreased,but were higher than those observed in the silicon rubber group.2.The damage to endometrium was obvious in IUD with copper.The damage to epithelium of endometrium in structure and function by IUD with indomethacin was found to be lower.

Towards a hybrid model-driven platform based on flux balance analysis and a machine learning pipeline for biosystem design

Metabolic modeling and machine learning(ML)are crucial components of the evolving next-generation tools in systems and synthetic biology,aiming to unravel the intricate relationship between genotype,phenotype,and the environment.Nonetheless,the comprehensive exploration of integrating these two frameworks,and fully harnessing the potential of fluxomic data,remains an unexplored territory.In this study,we present,rigorously evaluate,and compare ML-based techniques for data integration.The hybrid model revealed that the overexpression of six target genes and the knockout of seven target genes contribute to enhanced ethanol production.Specifically,we investigated the influence of succinate dehydrogenase(SDH)on ethanol biosynthesis in Saccharomyces cerevisiae through shake flask experiments.The findings indicate a noticeable increase in ethanol yield,ranging from 6%to 10%,in SDH subunit gene knockout strains compared to the wild-type strain.Moreover,in pursuit of a high-yielding strain for ethanol production,dual-gene deletion experiments were conducted targeting glycerol-3-phosphate dehydrogenase(GPD)and SDH.The results unequivocally demonstrate significant enhancements in ethanol production for the engineered strains Δsdh4Δgpd1,Δsdh5Δgpd1,Δsdh6Δgpd1,Δsdh4Δgpd2,Δsdh5Δgpd2,and Δsdh6Δgpd2,with improvements of 21.6%,27.9%,and 22.7%,respectively.Overall,the results highlighted that integrating mechanistic flux features substantially improves the prediction of gene knockout strains not accounted for in metabolic reconstructions.In addition,the finding in this study delivers valuable tools for comprehending and manipulating intricate phenotypes,thereby enhancing prediction accuracy and facilitating deeper insights into mechanistic aspects within the field of synthetic biology.

Histochemical study of transmyocardial laser channels in dogs

Objective Laser-induced myocardial injury was investigated in a canine transmyocardial laser revascularization model.Methods A total of 23 channels were created in the left ventricles of 5 animals with a CO2 laser. Four animals were sacrificed immediately and one at week 2. Lactate dehydrogenase and succinate dehydrogenase in channel regions were examined with a Nitro-BT method staining.Results Immediately after the procedure, laser channels and surrounding injured myocardium could be stratified from the center to the border into 5 concentric zones, i.e., vaporized zone, carbonized zone, enzyme-disappeared zone, enzyme-decreased zone and enzyme-concentrated zone. Two weeks later, the phenomenon disappeared.Conclusions Immediately after transmyocardial revascularization, there is a ring of enzyme-concentrated zone at the outermost region of injured myocardium. Two weeks later, enzyme activities of reversibly injured myocytes appear to have recovered.

Anti-aging effects of chlorpropamide depend on mitochondrial complex-Ⅱ and the production of mitochondrial reactive oxygen species

Sulfonylureas are widely used oral anti-diabetic drugs.However,its long-term usage effects on patients’lifespan remain controversial,with no reports of influence on animal longevity.Hence,the anti-aging effects of chlorpropamide along with glimepiride,glibenclamide,and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+(mito K-ATP)channels and mitochondrial complex II.Chlorpropamide delayed aging in Caenorhabditis elegans,human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice.In addition,the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms,which is consistent with the function of its reported targets,mito K-ATP channels.Increased levels of mitochondrial reactive oxygen species(mt ROS)were observed in chlorpropamide-treated worms.Moreover,the lifespan extension by chlorpropamide required complex II and increased mt ROS levels,indicating that chlorpropamide acts on complex II directly or indirectly via mito K-ATP to increase the production of mt ROS as a pro-longevity signal.This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C.elegans.

Effects of seawater immersion on the functions of mitochondria of myocardium and hepatocyte in hemorrhagic shock rats

Objective: To investigate the effects of seawater immersion on the function of myocardium and hepatocyte mitochondria in experimental hemorrhagic shock rats. Methods: Twenty-four male Wistar rats were divided into three groups (n=8 in each group): control group, HSL group (hemorrhagic shock group on land) and HSS group (hemorrhagic shock group in seawater). The hemodynamic parameters, activities of H+-ATPase (adenosinetriphosphatase), succinate dehydrogenase (SDH) and Ca 2+-Mg 2+-ATPase, the calcium contents in myocardium and hepatocyte mitochondria were measured and the changes of proton translocation across the inner mitochondrial membrane were analyzed. Results: The hemodynamic indexes and the activities of H+-ATPase, SDH, Ca 2+-Mg 2+-ATPase in HSS group were significantly lower than those in control group and HSL group (P< 0.05). In HSS group the calcium levels in tissue and mitochondria of myocardium and hepatocyte were elevated significantly compared with control group and HSL group(P< 0.05). There was no significant difference in proton translocation among three groups. Conclusions: This investigation demonstrates that seawater immersion can aggravate the conditions of hemorrhagic shock rats.

Variations of energy metabolism and adenosine Triphosphatase activity in gastric mucosa in chronic atrophic gastritis rats with Qi deficiency and blood stasis syndrome and effect of Zhiweifangbian capsule

OBJECTIVE: To study the effects of Zhiweifangbian (ZWFB) capsule on lactic dehydrogenase (LDH), succinic dehydrogenase (SDH) and ATPase activities in gastric mucosa of chronic atrophic gastritis (CAG) rats with Qi deficiency and blood stasis syndrome. METHODS: Totally 90 rats were randomly divided into 2 groups: normal group (n=10) and modelgroup (n=80). The CAG rat model of Qi deficiency and blood stasis type was induced by synthetic methods. After modeling for 12 weeks and the successful CAG model was determined, the CAG model rats were divided by random number table into model group (MG), ZWFB high-dose group (ZWFBH), ZWFB middle-dose group (ZWFBM), ZWFB low-dose group (ZWFBL) and Weimeisu group (WM), 9 rats in each group. The rats in the normal and model groups were intragastrically administrated with distilled water, 10 mL/kg every day; the ZWFB high-dose group with ZWFB, 0.6 g/ kg -1 · d -1 ; the ZWFB middle-dose group with ZWFB, 0.3 g/kg -1 · d -1 ; the ZWFB low-dose group with ZWFB, 0.15 g/kg -1 · d -1 , and the WM group with suspension of WM , 0.25 g/kg -1 · d -1 . The treatment was given for 90 consecutive days. Then general survival states were observed and the activities of LDH, SDH, Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase in gastric mucosa tissue were detected. RESULTS: Compared with the normal group, activity of LDH in the gastric mucosa (P<0.05) and activities of SDH, Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase significantly decreased in the normal group (P<0.05). Compared with the model group the activity of LDH decreased and activities of SDH, Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase significantly increased in the high dose ZWFB group (P<0.05). CONCLUSION: ZWFB capsule can promote energy metabolism and ATPase activity in the gastric mucosa cell, so as to protect the function of the gastric mucosa cell.