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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (11): 1136-1144.doi: 10.3736/jcim20081107

• Original Experimental Research • Previous Articles     Next Articles

Cordyceps mycelia extract decreases portal hypertension in rats with dimethylnitrosamine-induced liver cirrhosis: a study on its histological basis

Xian-bo Wang, Ping Liu(), Zhi-peng Tang, Feng-hua Li, Cheng-hai Liu, Yi-yang Hu, Lie-ming Xu   

  1. Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2008-05-07 Online:2008-11-20 Published:2008-11-15

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Objective: To study the effects of Cordyceps mycelia extract (CME) on portal hypertension in rats with dimethylnitrosamine (DMN) induced liver cirrhosis and probe into the mechanism of the action.
Methods: A rat model of liver cirrhosis was induced by peritoneal injection of DMN (at a dose of 10 μg/kg, once a day, 3 consecutive days per week) for 4 weeks. Other 15 rats were assigned into normal control group. The rats in CME-prevented group were administrated CME 0.74 g/(kg·d), once a day, simultaneously with DMN treatment and kept on 4-week administrating, and the rats in CME-treated group were administrated after the model was established. After 3-day, 2- and 4-week DMN injection and 2-, 4-week after the rat liver got cirrhosis, the pressure of portal vein (Ppv) was directly measured by intubation via tributary of vena mesenterica anterior. The serum hyaluronic acid (HA) content was measured by radioimmunoassay. The expressions of CD44, von Willebrand factor (vWF), laminin (LM), alpha-smooth muscle actin (α-SMA), type Ⅰ collagen (Col Ⅰ) and type Ⅳ collagen (Col Ⅳ) proteins in the hepatic sinusoidal walls were examined by immunohistochemistry.
Results: The caliber of portal vein (Cpv) and Ppv in the CEM group (after 4-week prevention) were significantly decreased as compared with those in the untreated group at the same point of time (P<0.05), also including serum HA content (P<0.05), and vWF, Col Ⅰ, Col Ⅳ, LM, α-SMA positive staining (P<0.05); however, CD44 positive staining were increased in the CEM group (P<0.05). The Cpv, Ppv and serum HA content were significantly decreased after 2-week CME treatment as compared with those in the untreated group (P<0.05). After 4-week CME treatment, the Cpv and Ppv in the CEM group were recovered to the normal level. After 2- and 4-week CME treatment, vWF, Col Ⅰ, LM and α-SMA positive stainings were decreased (P<0.05), and CD44 positive staining was increased (P<0.05) in the CME group as compared with those in the untreated group at the same point of time, but there were no marked changes found in Col Ⅳ staining.
Conclusion: CME plays a good role in preventing and treating the portal hypertension in rats with DMN-induced liver cirrhosis. The histological bases of the effects are to treat liver sinusoidal endothelial cell injury, inhibit hepatic stellate cell activation, inhibit and reverse hepatic sinusoida1 capillarization.

Key words: Cordyceps mycelia extract, portal hypertension, liver cirrhosis, liver sinusoidal endothelial cells, rat

CLC Number: 

  • R657.34

Table 1

Change of the caliber of portal vein in different groups（x±s, mm）"

Group n Caliber of portal vein
After 2-week prevention After 4-week prevention After 2-week treatment After 4-week treatment
Normal control 3 2.57±0.16 2.73±0.06 2.84±0.10 2.71±0.31
Untreated 5 2.94±0.12 3.45±0.25* 3.15±0.16* 3.07±0.16
CME 5 2.97±0.20* 2.92±0.53△ 2.80±0.23△ 2.95±0.18

Table 2

Change of the pressure of portal vein in different groups（x±s, mmHg）"

Group n Pressure of portal vein
After 2-week prevention After 4-week prevention After 2-week treatment After 4-week treatment
Normal control 3 7.54±0.22 6.78±0.09 6.02±0.62 6.89±0.36
Untreated 5 11.11±3.13* 14.81±1.42* 12.34±1.75* 8.68±1.80
CME 5 10.03±1.92* 11.74±1.02*△ 7.76±1.05△ 7.44±0.28

Table 3

Change of serum HA content in different groups（x±s, μg/L）"

Group n HA
After 3-day
prevention		 After 2-week
prevention		 After 4-week
prevention		 After 2-week
treatment		 After 4-week
treatment
Normal control 3 91.58±18.09 138.03±67.54 82.74±18.21 53.21±11.96 57.69±9.84
Untreated 5 987.35±457.23* 436.47±175.61*▲ 1 009.27±202.46* 109.62±36.5*□ 80.52±53.48□
CME 5 1 074.53±444.37* 340.66±144.98 356.29±161.69*△ 68.24±4.01*△ 57.09±8.56

Figure 1

Change of CD44 expression in the hepatic sinusoidal walls in different groups A: Expression of CD44 in the hepatic sinusoidal walls in rats was detected by immunohistochemical staining (Light microscopy, ×200). A1: Normal control group; A2: Untreated group (after 4-week DMN injection); A3: CME group (after 4-week CME prevention); A4: Untreated group (4 weeks after DMN injection); A5: CME group (after 4-week CME treatment). B: Comparison of the area ratio of CD44 positive staining of the hepatic sinusoidal walls in different observing times. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

Figure 2

Change of vWF expression in the hepatic sinusoidal walls in different groups A: Expression of vWF in the hepatic sinusoidal walls in rats was detected by immunohistochemical staining (Light microscopy, ×200). A1: Normal control group; A2: Untreated group (after 4-week DMN injection); A3: CME group (after 4-week CME prevention); A4: Untreated group (4 weeks after DMN injection); A5: CME group (after 4-week CME treatment). B: Comparison of the area ratio of vWF positive staining of the hepatic sinusoidal walls in different observing times. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

Figure 3

Change of α-SMA expression in the hepatic sinusoidal walls in different groups A: Expression of α-SMA in the hepatic sinusoidal walls in rats was detected by immunohistochemical staining (Light microscopy, ×200). A1: Normal control group; A2: Untreated group (after 4-week DMN injection); A3: CME group (after 4-week CME prevention); A4: Untreated group (4 weeks after DMN injection); A5: CME group (after 4-week CME treatment). B: Comparison of the area ratio of vWF positive staining of the hepatic sinusoidal walls in different observing times. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

Figure 4

Change of LM expression in the hepatic sinusoidal walls in different groups A: Expression of LM in the hepatic sinusoidal walls in rats was detected by immunohistochemical staining (Light microscopy, ×200). A1: Normal control group; A2: Untreated group (after 4-week DMN injection); A3: CME group (after 4-week CME prevention); A4: Untreated group (4 weeks after DMN injection); A5: CME group (after 4-week CME treatment). B: Comparison of the area ratio of LM positive staining of the hepatic sinusoidal walls in different observing times. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

Figure 5

Change of Col Ⅰexpression in the hepatic sinusoidal walls in different groups A: Expression of Col Ⅰ in the hepatic sinusoidal walls in rats was detected by immunohistochemical staining (Light microscopy, ×200). A1: Normal control group; A2: Untreated group (after 4-week DMN injection); A3: CME group (after 4-week CME prevention); A4: Untreated group (4 weeks after DMN injection); A5: CME group (after 4-week CME treatment). B: Comparison of the area ratio of Col Ⅰ positive staining of the hepatic sinusoidal walls in different observing times. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

Figure 6

Change of Col Ⅳexpression in the hepatic sinusoidal walls in different groups A: Expression of Col Ⅳ in the hepatic sinusoidal walls in rats was detected by immunohistochemical staining (Light microscopy, ×200). A1: Normal control group; A2: Untreated group (after 4-week DMN injection); A3: CME group (after 4-week CME prevention); A4: Untreated group (4 weeks after DMN injection); A5: CME group (after 4-week CME treatment). B: Comparison of the area ratio of Col Ⅳ positive staining of the hepatic sinusoidal walls in different observing times. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

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