Fengbaisan suppresses endoplasmic reticulum stress by up-regulating SIRT1 expression to protect rats with chronic obstructive pulmonary diseases.

CONTEXT: Our previous study found that Fengbaisan improved chronic obstructive pulmonary diseases (COPD). OBJECTIVE: To elucidate the mechanism of Fengbaisan in COPD. MATERIALS AND METHODS: Rats in Model, FBS, FBS + DMSO and FBS + EX527 groups received cigarette smoke extract (CSE) inhalation and intratracheal instillation of lipopolysaccharide to establish COPD model. Normal group received room air and normal saline. The COPD rats were given Fengbaisan (1 mL/d) or combined with EX527 (5 mg/kg/2 d) by intraperitoneal injection. Human lung carcinoma (A549) cells were treated with 10% CSE, 10% serum-containing Fengbaisan or EX527. We observed lung percentage of forced expiratory volume in first 0.3 sec to forced vital capacity (FEV0.3/FVC), inspiratory resistance (RI) and lung dynamic compliance (Cdyn) of rats. The lung pathological changes, the number of inflammatory cells and neutrophils, inflammatory factor, apoptosis, gene and protein expression were examined. RESULTS: SIRT1 was downregulated in lung tissues of COPD rats and CSE-induced A549 cells. Fengbaisan enhanced FEV0.3/FVC (74.28%) and Cdyn (0.28 cm H2O/mL/s), and reduced RI (0.48 mL/cm H2O) of COPD rats. Moreover, Fengbaisan promoted SIRT1 expression, and repressed TIMP-1/MMP-9 expression. Fengbaisan enhanced apoptosis and the expression of GRP78, caspase-12 and caspase-3. The inflammatory factor levels, the number of inflammatory cells and neutrophils, and lung lesions were inhibited by Fengbaisan in COPD rats. The influence conferred by Fengbaisan was abolished by EX527. DISCUSSION AND CONCLUSIONS: Fengbaisan inhibits endoplasmic reticulum stress and inflammation reaction by up-regulating SIRT1 expression to improve COPD. Therefore, Fengbaisan may be an effective Chinese medicine for treating COPD.

KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetic patients.

The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment. The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA-IR values (P < 0.01) than those with the A allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.

NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes.

AIMS: We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment. RESULTS: The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P < 0.05) (-8.20, -4.89 vs.-3.92, -1.20). CONCLUSIONS: The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.

Association of plasma epinephrine level with insulin sensitivity in metabolically healthy but obese individuals.

In the present study, we explored the association of catecholamines with insulin sensitivity in "metabolically healthy but obese" (MHO) individuals, by examining the metabolic characteristics and plasma catecholamine levels in 100 obese, sedentary postmenopausal women. Subjects were classified as MHO (n=25) or at-risk (n=25) based on the upper and lower quartiles of insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp technique. The MHO group presented a significantly higher range of plasma epinephrine levels (73 ± 21 pg/mL) than the at-risk group (39 ± 20 pg/mL) (P<0.05), though both within the normal basal range of plasma epinephrine (56 ± 30 pg/mL). Multivariate regression analysis showed that high-sensitivity C-reactive protein, plasma epinephrine, triglycerides and lean body mass index were independent predictors of glucose disposal. The plasma epinephrine level was positively correlated with the glucose disposal rate, insulin sensitivity and the HDL-cholesterol level, and negatively correlated with the triglycerides level (P<0.05). In conclusion, this study for the first time demonstrates a positive association between plasma epinephrine level and insulin sensitivity in MHO individuals.

Serine racemase rs391300 G/A polymorphism influences the therapeutic efficacy of metformin in Chinese patients with diabetes mellitus type 2.

1. The aim of this study was to investigate the association of the serine racemase (SRR) rs391300 G/A polymorphism with the risk of diabetes mellitus type 2 (T2DM) and to assess the impacts of the polymorphism on the therapeutic efficacy of metformin in Chinese patients. 2. A case-control study of 402 patients with T2DM and 171 healthy controls was conducted. The SRR rs391300 polymorphism was genotyped in all participants using the ABI 3700 automated sequencer. Forty-four recent-onset T2DM patients with different rs391300 genotypes were selected to receive 500 mg metformin orally daily for 12 consecutive weeks as monotherapy. Serum fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated haemoglobin (HbA1c), fasting serum insulin (FINS), postprandial serum insulin (PINS), triglycerol (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), homeostasis model assessment for insulin resistance (HOMA-IR), and body mass index (BMI) were determined before and after metformin treatment. 3. The distribution frequencies of rs391300 were in agreement with Hardy-Weinberg equilibrium (P > 0.05). After treatment with metformin, the values of BMI, FPG, PPG, PINS, HbA1c, CHO, and TG decreased significantly (P < 0.01), whereas FINS increased (P < 0.001), in patients with T2DM. Patients with the GA or AA genotype of rs391300 showed better improvements in the levels of FPG, PPG, and CHO (P < 0.05) than individuals with the GG genotype. 4. The SRR rs391300 polymorphism was associated with the therapeutic efficacy of metformin in Chinese patients with T2DM.

The protective effect of magnesium lithospermate B against glucose-induced intracellular oxidative damage.

OBJECTIVES: To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H(2)O(2), we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. MATERIALS AND METHODS: The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50µmol/L or 100µmol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. CONCLUSIONS: LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.

NAMPT -3186C/T polymorphism affects repaglinide response in Chinese patients with Type 2 diabetes mellitus.

1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy controls were genotyped for NAMPT-948G>T and -3186C>T polymorphisms. Thirty-five patients with different NAMPT -3186 C/T genotypes and the same organic anion-transporting polypeptide 1B1 (OATP1B1521) T/C genotype were randomly selected to undergo 8 weeks preprandial repaglinide treatment (1 mg, three times daily). Serum fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated haemoglobin (HbAlc), fasting serum insulin (FINS), post-prandial serum insulin (PINS), triglyceride (TG), total cholesterol (CHO), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined before and after repaglinide treatment. 3. After repaglinide treatment for 8 consecutive weeks, there were significantly decreases in PFG, PPG, HbAlc, CHO and LDL-C, and increases in FINS, HDL-C and the HDL-C : LDL-C ratio, in T2DM patients. The elevated PINS value in patients with CT genotypes was significantly lower than that in patients with the CC and TT genotypes (P < 0.05) and there were significant differences in CHO between patients with the CT genotype and the CC or TT genotype (P < 0.05). 4. The data suggest that the NAMPT -3186C>T polymorphism is significantly associated with plasma levels of PINS and CHO in Chinese T2DM patients with repaglinide monotherapy.

A systematic review of RCTs and quasi-RCTs on traditional Chinese patent medicines for treatment of chronic hepatitis B.

Traditional Chinese patent medicines (TCPMs) are widely used for treatment of chronic hepatitis B (CHB) in China. To estimate the overall effectiveness of TCPMs for CHB, we performed a systematic review of clinical reports designed as randomized controlled trials (RCTs). One hundred and thirty-eight available RCTs and quasi-RCTs on 62 TCPMs, involving 16,393 patients, were included. The methodological quality of these trials was generally "poor". Few trials (6.52%) reported the methods of randomization correctly. Another common problem was the lack of allocation concealment, proper blinding, and the reporting of lost cases and dropouts. Forty-two trials (30.43%) on 27 TCPMs reported some anti-viral effect of TCPMs. Others reported beneficial aspects, including improvements of liver function (79.71% of the studies), liver fibrosis (29.99%), and CHB symptoms (92.75%). Forty-one articles (29.71%) reported mild adverse events with TCPMs but these occurred infrequently. In summary, the outcome of the report on currently registered TCPMs may be biased due to poor methodology. The data from these trials, therefore, is too weak to use in forming a recommendation for treatment of CHB. Nevertheless, five drugs (Dan Shen agents, Da Huang Zhe Chong pill/capsule, Shuang Hu Qing Gan granule, Fu Zheng Hua Yu granule and Cao Xian Yi Gan capsule) appear to be more effective than the other TCPMs.

Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type 2 diabetes mellitus and repaglinide response in Chinese patients.

OBJECTIVE: Genome-wide association studies (GWASs) identified that SLC30A8 genetic polymorphism was a risk of type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients. METHODS: We conducted a case-control study of 443 T2DM patients and 229 healthy volunteers to identify SLC30A8 rs13266634 and rs16889462 genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-eight patients were randomly selected and underwent an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c) and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. RESULTS: SLC30A8 rs13266634 risk C allele frequency was higher in T2DM patients than in healthy controls (P < 0.05). There was a better repaglinide response on FINS (P < 0.05) and PINS (P < 0.01) in patients with rs13266634 CT+TT genotypes compared with CC genotype carriers. Patients with rs16889462 GA genotype showed an enhanced repaglinide efficacy on FPG (P < 0.01), PPG (P < 0.01) and HbAlc (P < 0.05) compared with GG genotype individuals. CONCLUSIONS: SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide therapeutic efficacy in Chinese T2DM patients.

IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population.

AIM: To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients. METHODS: A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment. RESULTS: The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects. CONCLUSION: The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients.

Effects of the peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) Thr394Thr and Gly482Ser polymorphisms on rosiglitazone response in Chinese patients with type 2 diabetes mellitus.

The objective was to investigate whether peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) Thr394Thr and Gly482Ser polymorphisms influence rosiglitazone response in Chinese patients with type 2 diabetes mellitus. Among the 241 patients enrolled in genotyping for PGC-1α Thr394Thr and Gly482Ser polymorphisms by polymerase chain reaction-restriction fragment length polymorphism assay, 41 patients with different Thr394Thr or Gly482Ser genotypes received oral rosiglitazone (4 mg/d) for 12 consecutive weeks. Carriers of A allele of Thr394Thr had high density lipoprotein-cholesterol that was enhanced to a lesser degree and smaller attenuated postprandial serum insulin compared with G alleles (P < .05), and patients with PGC-1α Gly482Gly had fasting plasma glucose that was attenuated to a greater degree (P < .01) and postprandial serum insulin (P < .05) compared with Gly482Ser+Ser482Ser. After rosiglitazone treatment, carriers of A allele of Thr394Thr and Ser allele of Gly482Ser showed a trend in worsening for GG (P < .05) and a significant therapeutic response to rosiglitazone for Gly/Gly (P < .05). These data suggest that the PGC-1α Thr394Thr and Gly482Ser polymorphisms are associated with therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with type 2 diabetes mellitus.

Impact of rosiglitazone on the expression of beta3-AR in the stable cell lines expressed beta3-AR gene.

BACKGROUND: The aim of the present study was to investigate the effect of rosiglitazone, a peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2) agonist, on the expression of beta3-adrenergic receptor (beta3-AR) at transcriptional and translational level. METHODS: We cloned the cDNA sequences of human PPAR-gamma2 (hPPAR-gamma2) gene and human wild type and mutant beta3-adrenergic receptor (hbeta3-AR) genes and established their eukaryotic expression vectors. The pcDNA3.1/hbeta3-AR (mutant and wild type) was transfected into SH-SY5Y cells using electroporation method. The expression level of beta3-AR protein was determined by Western blot analysis. RESULTS: Our results showed that the reverse transcription-PCR products were consistent with theoretical fragment sizes of human PPAR-gamma2 (1544 bp) and human beta3-AR genes (1578 bp). The sequence analysis of PPAR-gamma2 and beta3-AR genes showed that the fragment sizes were the same as that of human PPAR-gamma2 and human beta3-AR genes in Genbank. The pcDNA3.1/hbeta3-AR (mutant and wild type) was successfully cloned to SH-SY5Y cells. We found that the expression of beta3-AR protein was significantly inhibited by rosiglitazone in a concentration-dependent manner in SH-SY5Y cell lines stably expressed beta3-AR genes. CONCLUSIONS: The results suggest that rosiglitazone has a concentration-dependent inhibitory effect on the expression of beta3-AR protein, and this inhibitory effect may be due to activation of PPAR-gamma2 receptor.

The genetic polymorphisms of beta3-adrenergic receptor (AR) Trp64Arg and beta2-AR Gln27Glu are associated with obesity in Chinese male hypertensive patients.

BACKGROUND: Genetic polymorphisms of beta3-adrenergic receptor (AR) Trp64Arg and beta2-AR Gln27Glu may result in significant change in the functions of these receptors. The aims of the present study were to investigate the association between Trp64Arg, Arg16Gly and Gln27Glu polymorphisms and the susceptibility to obesity and hypertension in a Chinese population. METHODS: A total of 437 Chinese subjects including 149 obese hypertensive patients, 139 non-obese essential hypertensive patients, and 149 non-obese normotensive healthy controls were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific (AS)-PCR assays were used to identify Trp64Arg, Arg16Gly, and Gln27Glu genotypes. RESULTS: The allele frequencies of 64Arg and 27Glu in the obese hypertensive group were 0.178 and 0.128, respectively. Both were significantly higher than in the non-obese hypertensive and the control groups (p<0.05). Further analysis showed that this association existed only in male hypertensive patients. CONCLUSIONS: These data reveal that frequencies of beta3-AR 64Arg and beta2-AR 27Glu were significantly higher in our obese hypertensive patients than in the non-obese hypertensive population and healthy controls. beta3-AR Trp64Arg and beta2-AR Gln27Glu genetic polymorphisms are associated with obesity in Chinese male hypertensive patients.

Effect of Jianweiyuyang granule on gastric ulcer recurrence and expression of VEGF mRNA in the healing process of gastric ulcer in rats.

AIM: To investigate the effect of Jianweiyuyang (JWYY) granule on gastric ulcer recurrence and its mechanism in the treatment of gastric ulcer in rats. METHODS: Gastric ulcer in rats was induced according to Okeba's method with minor modification and the recurrence model was induced by IL-1beta. The expression of vascular endothelial growth factor mRNA (VEGF mRNA) was examined by reverse transcription polymerase chain reaction in gastric ulcer and microvessel density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. RESULTS: MVD was higher in the JWYY treatment group (14.0+/-2.62) compared with the normal, model and ranitidine treatment groups (2.2+/-0.84, 8.8+/-0.97, 10.4+/-0.97) in rats (P<0.01). The expression level of VEGF mRNA in gastric tissues during the healing process of JWYY treatment group rats significantly increased compared with other groups (normal group: 0.190+/-0.019, model group: 0.642+/-0.034, ranitidine group: 0.790+/-0.037, P<0.01). CONCLUSION: JWYY granules can stimulate angiogenesis and enhance the expression of VEGF mRNA in gastric ulcer rats. This might be the mechanism for JWYY accelerating the ulcer healing, and preventing the recurrence of gastric ulcer.

[Therapeutic effects of the combination of traditional Chinese medicine and western medicine on patients with peptic ulcers].

OBJECTIVE: To explore the therapeutic effects and mechanisms of the combination of traditional Chinese medicine and western medicine on patients with peptic ulcers. METHODS: One hundred and twenty patients were randomly divided into 6 groups. Another 10 patients as the control group were confirmed with no peptic ulcers by endoscope, but had digestive tract symptoms. The clinical effects were compared among each group after the one month treatment. RESULTS: The clinical effects of the combination of Jianweiyuyang granules and ranitidine capsules were better than those of western medicine, with improvement in symptoms and syndrome (P < 0.01 to 0.05), but there was not significant difference with the rate of ulcer healing and the Hp clearance among the combination of Jianweiyuyang granules and ranitidine capsules, Jianweiyuyang granules, and ranitidine capsules (P > 0.05). The combination of Jianweiyuyang granules and ranitidine capsules could significantly upregulate the expression of MUCSAC mRNA (P < 0.01), while downregulate the expression of ETAR mRNA (P < 0.01). CONCLUSION: There is obvious advantage in treating peptic ulcers by the combination of Jianweiyuyang granules and ranitidine capsules, and its mechanisms may be to protect the gastric mucosal barrier by up-regulating the expression of MUCSAC mRNA and to improve the gastric mucosal blood flow by down-regulating the expression of ETAR mRNA.