The Study Of Pharmacodynamics Of Buzhong Yiqi Decoction With Its Compatibility Mechanism

ObjectiveBuzhong Yiqi Decoction(BZYQD), which follows the principle of "Neijing" warming the exhaustion and replenishing the deficiency, is first from the Chinese Jin Dynasty Li Dongyuan "Topic of the spleen and stomach ".The compatibility of BZYQD is strict and drug options are exact. Tonifying qi and invigorating yang is the most characteristic compatibility in BZYQD, and many clinical observations have proved its outstanding effects to the the spleen deficiency syndrome. Otherwise, large experimental studies also show that BZYQD could regulate the gastrointestinal function, enhance immunity and protect gastric mucosa, but its mechanism is lack of in-depth research.Our studies focus on the mechanism of BZYQD and its compatibility with tonifying qi and invigorating yang. From the view of pharmacological effect, internal hormone and molecular biology, We try to analyse the correlation among compatibility of tonifying qi and invigorating yang, pharmacodynamics and its action of mechanism, for exploring the scientific connotation of tonifying qi and invigorating yang, replenishing the former researches and providing scientific basis for clinical practices and further experimental study.Methods1. Study on the Effect of Tonifying Qi and Invigorating Yang in BZYQD to the Mice with Spleen DeficiencyModel of mice with spleen deficiency was copied by an compounding method—administration of Rheum Palmatum L, strength sapping by swimming, and starvation. Successfully copied models were randomly divided into group of BZYQD, group of drug pair of Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri, group of BZYQD without Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri, group of negative control and group of normal control. Respectively dosing the groups for a week, the mice were tested on their anti-cold and anti-fatigue function, other effects as hymic index, splenic index and gastrointestinal propulsion were observed from five groups.2. Study on the Pharmacological Effect of Tonifying Qi and Invigorating Yang in BZYQD to the Rat with Spleen DeficiencyModel of rat with spleen deficiency was copied by an compounding method—administration of Rheum Palmatum L, strength sapping by swimming, and starvation. Successfully copied models were randomly divided into group of BZYQD, group of drug pair of Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri, group of BZYQD without Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri, group of negative control and group of normal control. Dosing for14days, blood flows of gastric mucosia (GMBF),level of creatine kinase(CK), serum concentration of D-xylose,activity of amylase(AMS) and content of gastrin(GAS) were measured, respectively.3. Effect of Tonifying Qi and Invigorating Yang in BZYQD on GAS Expression to the Rat with Spleen DeficiencyModel of rat with spleen deficiency was copied by an compounding method—administration of Rheum Palmatum L, strength sapping by swimming, and starvation. Successfully copied Sprague Dawley rats were randomly divided into group of BZYQD, group of drug pair of Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri, group of BZYQD without Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri, group of negative control and group of normal control. Respectively dosing for14days, rats were executed to take the stomach and cut gastric antrum upside the ice.The lever of GAS mRNA was detected by reverse transcription-polymerase chain reaction(RT-PCR).4. Effect of Tonifying Qi and Invigorating Yang in BZYQD on the Protein Expression of Rrefoil Factor1(TFF1) to the Rat with Spleen DeficiencyModel of rat with spleen deficiency was copied by an compounding method—administration of Rheum Palmatum L, strength sapping by swimming, and starvation. Successfully copi ed Sprague Dawley rats were randomly divided into group of BZYQD, group of drug pair of Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri, group of BZYQD without Leguminosae-Rhizoma Cimicifugae and Radix Bupleuri,group of negative control and group of normal control.Respectively dosing for14days, rats were executed to take the stomach and cut it off through the greater gastric curvature, douche the gastric mucosa with0.9%NaCl,clip the same pathlogical part, and then fix in the10%neutral Formalin buffer. The change of protein expression of TFF1was examined by immunohistochemistry.Results1. Group of BZYQD, group of drug pair of Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri, and group of BZYQD without Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri could improve the mice anti-fatigue function, hymic index, splenic index and gastrointestinal propulsive rate, but the ability of anti-cold did less change in the last two groups.2. Group of BZYQD could effectively increase the five experimental indexes of GMBF, CK, D-xylose, AMS, GAS in rats. However, group of drug pair of Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri, and group of BZYQD without Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri did little impact on the above five indexes except AMS.3. Group of BZYQD could effectively improve the expression of GAS mRNA in rats with spleen deficiency, but group of drug pair of Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri, and group of BZYQD without Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri did little impact on it.4. Group of BZYQD could up-regulate the expression of TFF1in rats with spleen deficiency, but no significant difference was found in group of drug pair of Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri, and group of BZYQD without Radix Astragali-Rhizoma Cimicifugae and Radix Bupleur.ConclusionGastrointestinal tract, filled with endocrine cells which secrete gastrointestinal hormone, is the largest endocrinal organ in human body. Gastrointestinal hormone could regulate the digestive tract’s function of secretion, moving, absorption, bloodstream and cytotrophy, and various kinds of clinical symptoms and syndrome will be induced when the functions of digestive tract change accompanied with the hormone imbalance. GAS is secreted by G-cell in gastric antrum and proximal duodenal mucosa, with main physical function of promoting the secretion of gastric acid, increasing the blood flow of gastric mucosa and nourishing the gastrointestinal mucosa. It is very important for keeping the physiological function of gastric mucosa with the regular blood cycling, and basic researches have proved that BZYQD has the function of tonifying the spleen and invigorating yang, also takes great part in immunoregulation.Motherland medicine thinks that the stomach governs receiving and digesting food, while the spleen governs transportation and transformation of the essence of water and food. The normal function of spleen and stomach ensures the normal production and transformation of qi and blood, which provide nutriment to the organism, and nourish viscera, tissue and organ, based on that, the body physiological functions can work regularly. When spleen deficiency appears, the secretion of AMS is insufficient, natually,the absorption of nutriment will be affected. D-xylose is a kind of pentose, after oral administration, it is absorbed by duodenum and jejunum through facilitated diffusion, in this course it needs to consume energy, and is related to Na+-K+-ATP enzyme existing in the surface of cytomembrane. When spleen deficiency appears, the activity of Na+-K+-ATP enzyme decreases so that the absorption of D-xylose descends, for villous with the function of absorption in small intestinal mucosa shortening in longevity and length and reducing in number. The reversible reaction that CK catalyzes the energy-rich phosphate bond between ATP and creatine in vivo and transforms it into phosphocreatine and ADP, provides energy for muscle contraction and transporting systerm. In the animal model with spleen deficiency induced by abnormal diet, ATP energy supplying is relatively insufficient so that the activity of CK in blood decreases to reduce its disintegration and energy expenditure. TFF1,a Low-molecule polypeptide secreted by epithelial cell, mainly distributes in gastric mucosa. TFF1has the vital protective action for gastrointestinal mucosa, and can promote the damaged mucosa reconstruction and repair by inhibiting cell proliferation and and apoptosis. From the point of how BZYQD and its compatibility of tonifying qi and invigorating yang do influence on the expression of GAS mRNA and protein expression of TFF1, our study try to discuss the mechanism of BZYQD in treating spleen deficiency syndrome,which makes theoretical significance for explaining the pathological mechanism of spleen deficiency syndrome and the compatibility mechanism of BZYQD.Our study show that the related experimental effects, including anti-cold and anti-fatigue function, hymic index, splenic index and gastrointestinal propulsive rate in mice with spleen deficiency, as well as GMBF, CK,1)-xy lose, AMS, TFF1and GAS in rats with spleen deficiency are descending signi ficantly, which suggests the defense and absorption fuction of gastric mucosa decreases when the spleen deficiency appears. Treated by BZYQD, all of the above indexes up-regulate significantly, which suggests that BZYQD can increase the expression of gastrointestinal hormone, enhance the barrier protection of gastric mucosa and accelerate the repair for gastric mucosa cells by rising the expression of TFF1.To some extent, it reflects the multi-targeted and multi-level function characteristics of Chinese medicine formulae, but group of drug pair of Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri, and group of BZYQD without Radix Astragali-Rhizoma Cimicifugae and Radix Bupleuri do less effect on animal models with spleen deficiency except the experimental indexes of anti-fatigue function, hymic index, splenic index, gastrointestinal propulsive rate and AMS.BZYQD is an effective prescription mainly comprised by drugs of tonifying qi and that of invigorating yang. As the experimental results showed above, compared with BZYQD, the related pharmacological effects of both decoction without drugs of invigorating yang and only with this compatibility are decreased obviously, which suggests the rationality of BZYQD with its compatibility mechanism of tonifying qi and invigorating yang further.