Narrow Results

Damp obstruction refers to the stagnation of vital energy (qi) caused by dampness resulting in dysfunction of body and limbs movement, as well as impairment of spleen and stomach digestive function. Damp obstruction is the dampness-induced imbalance of five elements; thus it serves as an ideal model for genomic study using cDNA microarray. We have performed microarray analyses to major organs of damp-obstructed rats. Cluster analysis for the expression profiles of major organs indicated that spleen, stomach, and kidney respond to dampness differently from heart, liver, lung, and brain. Gene expression profile specific to each element or group of elements was also identified. Our results are consistent with the philosophy of Chinese medicine that the five elements, metal (lung), wood (liver), water (kidney), fire (heart), and earth (spleen and stomach) coordinate by subjugation or restriction to maintain a healthy, physiological state. This is the first time that a powerful genomic tool was applied to probe the ancient theory of Chinese medicine.

Functional and molecular characterization was performed on the major organs of damp-obstructed rats by applying expression datasets of microarray experiments and real-time RT-PCR. Gene ontology repertoires, i.e. cellular component, molecular function, and biological process were used to classify differentially expressed genes in the major organs of rats upon treatment of dampness. As to the cellular component, over-expression of genes associated with the plasma membrane was observed in the stomach, spleen, kidney, heart, liver, and lung. Genes associated with translational machinery, endoplasmic recticulum membrane, Golgi apparatus, and nuclear envelope were down-regulated in the stomach. Concerning the molecular function, genes associated with oxidoreductase activity were up-regulated in the stomach, spleen, kidney, lung, and brain. Channel activity, membrane receptor, and electron transporter activity were up-regulated in stomach, kidney, and lung. Regarding the biological process, genes associated with signal transduction were up-regulated in the stomach, while genes associated with biosynthesis and ATP metabolism were down-regulated. In the spleen, melanin biosynthesis was up-regulated while hormone-related activities were down-regulated. In the kidney, genes associated with nucleotide biosynthesis and ATP metabolism were depressed. In the heart and liver, apoptosis was up-regulated while immune response and RAS signal transduction were down-regulated. Interestingly, genes associated with oncogenesis were up-regulated in the stomach and kidney. Functional fingerprints indicated that dampness weakened membrane structures, depressed metabolic activity (especially ATP metabolism), damaged matrix proteins, enhanced signal transduction, and revealed a positive association with oncogenesis. To quantify the functional impact at the molecular level, mRNA levels of key genes were determined by real-time RT-PCR. The results indicated that ATP storage in kidney, spleen, and stomach was depleted in damp-obstructed rats. We propose that oxidative stress, membrane integrity, melanin biosynthesis, ion channel activity, and ATP metabolism might be hallmarks for damp-obstructed rats. Our results also suggested dampness as a pathogenic factor in rats which is possibly associated with enhanced liabilities of cancer.